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Disorders of sex development v4.1 Sarah Leigh Panel version 4.0 has been signed off on 2023-03-22
Disorders of sex development v4.0 Sarah Leigh promoted panel to version 4.0
Disorders of sex development v3.3 FGFR2 Arina Puzriakova Tag Q2_21_expert_review was removed from gene: FGFR2.
Disorders of sex development v3.3 HHAT Arina Puzriakova Tag Q4_21_rating was removed from gene: HHAT.
Disorders of sex development v3.3 NR3C1 Arina Puzriakova Tag Q2_21_rating was removed from gene: NR3C1.
Disorders of sex development v3.3 NR2F2 Arina Puzriakova Tag Q2_21_rating was removed from gene: NR2F2.
Disorders of sex development v3.3 MYRF Arina Puzriakova Tag Q2_21_rating was removed from gene: MYRF.
Disorders of sex development v3.3 HOXA13 Arina Puzriakova Tag Q2_21_rating was removed from gene: HOXA13.
Disorders of sex development v3.3 GATA4 Arina Puzriakova Tag Q2_21_rating was removed from gene: GATA4.
Disorders of sex development v3.3 CYP11A1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: CYP11A1.
Disorders of sex development v3.3 CTU2 Arina Puzriakova Tag Q2_21_rating was removed from gene: CTU2.
Disorders of sex development v3.3 NR3C1 Arina Puzriakova Source Expert Review Green was added to NR3C1.
Source NHS GMS was added to NR3C1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v3.3 NR2F2 Arina Puzriakova Source Expert Review Green was added to NR2F2.
Source NHS GMS was added to NR2F2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v3.3 MYRF Arina Puzriakova Source Expert Review Green was added to MYRF.
Source NHS GMS was added to MYRF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v3.3 HOXA13 Arina Puzriakova Source Expert Review Green was added to HOXA13.
Source NHS GMS was added to HOXA13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v3.3 GATA4 Arina Puzriakova Source Expert Review Green was added to GATA4.
Source NHS GMS was added to GATA4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v3.3 CYP11A1 Arina Puzriakova Source NHS GMS was added to CYP11A1.
Mode of inheritance for gene CYP11A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of sex development v3.3 CTU2 Arina Puzriakova Source Expert Review Green was added to CTU2.
Source NHS GMS was added to CTU2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v3.2 HHAT Arina Puzriakova commented on gene: HHAT
Disorders of sex development v3.2 NR3C1 Arina Puzriakova reviewed gene: NR3C1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v3.2 NR2F2 Arina Puzriakova reviewed gene: NR2F2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v3.2 MYRF Arina Puzriakova reviewed gene: MYRF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v3.2 HOXA13 Arina Puzriakova reviewed gene: HOXA13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v3.2 GATA4 Arina Puzriakova reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v3.2 CYP11A1 Arina Puzriakova commented on gene: CYP11A1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Disorders of sex development v3.2 CTU2 Arina Puzriakova reviewed gene: CTU2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Disorders of sex development v3.0 Catherine Snow promoted panel to version 3.0
Disorders of sex development v2.66 FGFR2 Eleanor Williams commented on gene: FGFR2
Disorders of sex development v2.66 PRDM13 Ivone Leong Tag watchlist tag was added to gene: PRDM13.
Disorders of sex development v2.66 PRDM13 Ivone Leong Added comment: Comment on publications: New publication: 35390279.
Publication reported eight individuals from four families of different origins with loss-of-function PRDM13 variants. Phenotypic findings included cerebellar hypoplasia and perinatal lethality associated with severe brainstem dysfunctions (e.g., feeding and respiratory difficulties, central apnea, bradycardia). The patients were too young to determine if disorders of sexual development was present. Therefore gene should still stay Amber.
Disorders of sex development v2.66 PRDM13 Ivone Leong Publications for gene: PRDM13 were set to 34730112
Disorders of sex development v2.65 PRDM13 Ivone Leong Classified gene: PRDM13 as Amber List (moderate evidence)
Disorders of sex development v2.65 PRDM13 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. Based on the expert review and evidence there is currently not enough evidence to support a gene-disease association. This gene has been given an Amber rating.
Disorders of sex development v2.65 PRDM13 Ivone Leong Gene: prdm13 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.64 PRDM13 Ivone Leong Phenotypes for gene: PRDM13 were changed from congenital hypogonadotropic hypogonadism, MONDO:0015770 to congenital hypogonadotropic hypogonadism, MONDO:0015770; Cerebellar dysfunction, impaired intellectual development, and hypogonadotropic hypogonadism, OMIM:619761
Disorders of sex development v2.63 ZFPM2 Arina Puzriakova Phenotypes for gene: ZFPM2 were changed from 46XY sex reversal 9 616067 to 46XY sex reversal 9, OMIM:616067
Disorders of sex development v2.62 SRY Eleanor Williams commented on gene: SRY
Disorders of sex development v2.62 CYP11B1 Arina Puzriakova Phenotypes for gene: CYP11B1 were changed from Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, 202010 to Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency, OMIM:202010; Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN)
Disorders of sex development v2.61 CYP11A1 Arina Puzriakova Tag Q3_22_MOI tag was added to gene: CYP11A1.
Disorders of sex development v2.61 CYP11A1 Arina Puzriakova Publications for gene: CYP11A1 were set to 19116240; 18182448
Disorders of sex development v2.60 CYP11A1 Arina Puzriakova Added comment: Comment on mode of inheritance: Homozygous, compound heterozygous, and heterozygous (although most rare) variants in the CYP11A1 gene have all been associated with disease. Therefore, MOI should be updated to 'Both mono- and biallelic' at the next GMS panel update.
Disorders of sex development v2.60 CYP11A1 Arina Puzriakova Mode of inheritance for gene: CYP11A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Disorders of sex development v2.59 ISCA-37401-Loss Ivone Leong commented on Region: ISCA-37401-Loss: The required percent of overlap for this region has been changed from 80% to 60% following NHS Genomic Medicine Service approval.
Disorders of sex development v2.59 ISCA-37401-Loss Arina Puzriakova Required Overlap Percentage for ISCA-37401-Loss was changed from 80 to 60.
Disorders of sex development v2.58 ISCA-46302-Gain Arina Puzriakova Tag for-review was removed from Region: ISCA-46302-Gain.
Disorders of sex development v2.58 ISCA-46302-Gain Arina Puzriakova Classified Region: ISCA-46302-Gain as Green List (high evidence)
Disorders of sex development v2.58 ISCA-46302-Gain Arina Puzriakova Region: isca-46302-gain has been classified as Green List (High Evidence).
Disorders of sex development v2.57 ISCA-46302-Gain Arina Puzriakova commented on Region: ISCA-46302-Gain
Disorders of sex development v2.57 TSPYL1 Ivone Leong Tag for-review was removed from gene: TSPYL1.
Disorders of sex development v2.57 PPP1R12A Ivone Leong Tag for-review was removed from gene: PPP1R12A.
Disorders of sex development v2.57 DHX37 Ivone Leong Tag for-review was removed from gene: DHX37.
Disorders of sex development v2.57 TSPYL1 Ivone Leong commented on gene: TSPYL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Disorders of sex development v2.57 PPP1R12A Ivone Leong commented on gene: PPP1R12A
Disorders of sex development v2.57 DHX37 Ivone Leong commented on gene: DHX37
Disorders of sex development v2.56 TSPYL1 Ivone Leong Source Expert Review Green was added to TSPYL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v2.56 PPP1R12A Ivone Leong Source Expert Review Green was added to PPP1R12A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v2.56 DHX37 Ivone Leong Source Expert Review Green was added to DHX37.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Disorders of sex development v2.55 PRDM13 Zornitza Stark gene: PRDM13 was added
gene: PRDM13 was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: PRDM13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRDM13 were set to 34730112
Phenotypes for gene: PRDM13 were set to congenital hypogonadotropic hypogonadism, MONDO:0015770
Review for gene: PRDM13 was set to AMBER
Added comment: Recessive disease causing ID and DSD described in three unrelated families (2 consanguineous), but all are from Malta, and all share the same 13bp deletion spanning an exon-intron boundary, so likely founder effect.

Mouse KO is embryonically lethal, and tissue specific KO failed to replicate many of the patients phenotypes, other than hypoplasia of the cerebellar vermis and hemispheres.
Sources: Literature
Disorders of sex development v2.55 HHAT Eleanor Williams Phenotypes for gene: HHAT were changed from 46,XY DSD with chondrodysplasia to 46,XY DSD with chondrodysplasia; Nivelon-Nivelon-Mabille syndrome, OMIM:600092
Disorders of sex development v2.54 HHAT Eleanor Williams Publications for gene: HHAT were set to 24784881
Disorders of sex development v2.53 HHAT Eleanor Williams Classified gene: HHAT as Amber List (moderate evidence)
Disorders of sex development v2.53 HHAT Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber but with a recommendation for green rating following GMS review. 2 cases reported with 46, XY karyotype and sex reversal, plus a supportive mouse model.
Disorders of sex development v2.53 HHAT Eleanor Williams Gene: hhat has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.52 HHAT Eleanor Williams Tag Q4_21_rating tag was added to gene: HHAT.
Disorders of sex development v2.52 HHAT Eleanor Williams reviewed gene: HHAT: Rating: GREEN; Mode of pathogenicity: None; Publications: 24784881, 30912300, 33749989; Phenotypes: Nivelon-Nivelon-Mabille syndrome, OMIM:600092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of sex development v2.52 AR Arina Puzriakova Phenotypes for gene: AR were changed from Gender Assignment Gene Panel UKGTN; Androgen insensitivity, OMIM:300068; Androgen insensitivity,partial,with/without breast cancer, OMIM:312300; Hypospadias 1,X-linked, OMIM:300633 to Androgen insensitivity, OMIM:300068; Androgen insensitivity, partial, with or without breast cancer, OMIM:312300; Hypospadias 1, X-linked, OMIM:300633
Disorders of sex development v2.51 CYP19A1 Arina Puzriakova Phenotypes for gene: CYP19A1 were changed from Gender Assignment Gene Panel (UKGTN); Endocrine disorders including disorders of sexual development; Aromatase deficiency, 613546 to Aromatase deficiency, OMIM:613546
Disorders of sex development v2.50 CYP11A1 Arina Puzriakova Phenotypes for gene: CYP11A1 were changed from Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, 613743 to Adrenal insufficiency, congenital, with 46XY sex reversal, partial or complete, OMIM:613743
Disorders of sex development v2.49 ATP6V0A4 Arina Puzriakova Phenotypes for gene: ATP6V0A4 were changed from Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); Renal tubular acidosis, distal, autosomal recessive, 602722 to Genital Anomalies and Suspected Adrenal Problems Gene Panel (UKGTN); Distal renal tubular acidosis 3, with or without sensorineural hearing loss, OMIM:602722
Disorders of sex development v2.48 ATRX Eleanor Williams commented on gene: ATRX
Disorders of sex development v2.48 AR Arina Puzriakova Phenotypes for gene: AR were changed from Gender Assignment Gene Panel UKGTN; Androgen insensitivity,300068; Androgen insensitivity,partial,with/without breast cancer,312300; Hypospadias 1,X-linked,300633 to Gender Assignment Gene Panel UKGTN; Androgen insensitivity, OMIM:300068; Androgen insensitivity,partial,with/without breast cancer, OMIM:312300; Hypospadias 1,X-linked, OMIM:300633
Disorders of sex development v2.47 CTU2 Ivone Leong Entity copied from Severe microcephaly v2.146
Disorders of sex development v2.47 CTU2 Ivone Leong gene: CTU2 was added
gene: CTU2 was added to Disorders of sex development. Sources: Expert Review Amber,Expert list
Q2_21_rating tags were added to gene: CTU2.
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 26633546; 27480277; 31301155
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, OMIM:618142
Disorders of sex development v2.46 WNT2B Ivone Leong gene: WNT2B was added
gene: WNT2B was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: WNT2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT2B were set to 29909964; 33526876
Phenotypes for gene: WNT2B were set to Diarrhoea 9, OMIM:618168; 46,XX testicular disorder of sex development, MONDO:0100249
Review for gene: WNT2B was set to RED
Added comment: This gene is associated with a phenotype in OMIM but not Gene2Phenotype. This gene is also present on the Intestinal failure panel (Version 1.28).

Review submitted by Zornitza Stark on the Intestinal failure panel:
"Diarrhoea-9 is a form of neonatal-onset chronic diarrhoea characterized by an osmotic diarrhoea that is not substrate specific, abnormal crypt and villus architecture, and significant fat malabsorption. Three probands from two unrelated families and functional data suggesting severe intestinal dysregulation due to decreased intestinal stem cell number and function. Borderline Green/Amber. Sources: Expert Review
Zornitza Stark (Australian Genomics), 4 Jan 2021"

PMID: 33526876 reports an additional unrelated case. Patient is of Haitian descent (previous cases described in PMID:29909964 are of Vietnamese and Kuwaiti origins). Patient has neonatal onset diarrhoea with metabolic acidosis and failure to thrive. Patient also has bilateral microcornea and corneal clouding. Patient also presented with ambiguous genitalia and diagnosed with 46,XX testicular DSD. The authors reviewed the clinical findings of the previous patients they had reported on (PMID:29909964) and found that the Kuwaiti patients had bilateral microcornea, corneal neovascularization and thick corneas (I-2), and bilateral iridocorneal adhesions, congenital cataract, and iris coloboma (I-3). The gonadal findings in the Haitian patient was not seen in any of the other affected patients.

As there is only 1 case, this gene has been added as Red on this panel.
Sources: Literature
Disorders of sex development v2.45 FGFR2 Ivone Leong Tag Q2_21_expert_review tag was added to gene: FGFR2.
Disorders of sex development v2.45 FGFR2 Ivone Leong Classified gene: FGFR2 as Amber List (moderate evidence)
Disorders of sex development v2.45 FGFR2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype.

After consulting with the Genomics England Clinical Team, it was decided that this gene should be rated Amber. Helen Brittain (Genomics England):
"In the fetal cases the potential DSD phentoype is very mild and eclipsed by the skeletal / craniosynostosis presentation."
Disorders of sex development v2.45 FGFR2 Ivone Leong Gene: fgfr2 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.44 NR3C1 Ivone Leong Publications for gene: NR3C1 were set to 30158362; 31995340; 19933394; 7683692; 11932321; 31145715
Disorders of sex development v2.43 NR3C1 Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark. This gene is associated with a phenotype in OMIM but not in Gene2Phenotype.

PMID:30158362 reviewed 23 index cases of patients with variants in NR3C1. There are 33 index cases as of June 2019 (PMID:31995340). PMID:30158362 found that 63% of cases showed hyperandrogenism and impaired fertility (ambiguous genitalia, hirsutism and oligomenorrhoea in females; precocious puberty and oligospermia in males). 50% cases showed hyperaldosteronism, with or without hypertensionand/or hypokalemia.

There are also 4 biallelic cases (PMID:19933394; 7683692; 11932321; 31145715).

There is enough evidence to support a gene-disease association. Therefore this gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark. This gene is associated with a phenotype in OMIM but not in Gene2Phenotype.

PMID:30158362 reviewed 23 index cases of patients with variants in NR3C1. There are 33 index cases as of June 2019 (PMID:31995340). PMID:30158362 found that 63% of cases showed hyperandrogenism and impaired fertility (ambiguous genitalia, hirsutism and oligomenorrhoea in females; precocious puberty and oligospermia in males). 50% cases showed hyperaldosteronism, with or without hypertensionand/or hypokalemia.

There is enough evidence to support a gene-disease association. Therefore this gene should be rated Green at the next review.
Disorders of sex development v2.43 NR3C1 Ivone Leong Mode of inheritance for gene: NR3C1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of sex development v2.42 NR3C1 Ivone Leong Mode of inheritance for gene: NR3C1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Disorders of sex development v2.41 NR3C1 Ivone Leong Mode of inheritance for gene: NR3C1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Disorders of sex development v2.40 NR3C1 Ivone Leong Publications for gene: NR3C1 were set to 30158362
Disorders of sex development v2.39 NR3C1 Ivone Leong Classified gene: NR3C1 as Amber List (moderate evidence)
Disorders of sex development v2.39 NR3C1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. This gene is associated with a phenotype in OMIM but not in Gene2Phenotype.

PMID:30158362 reviewed 23 index cases of patients with variants in NR3C1. There are 33 index cases as of June 2019 (PMID:31995340). PMID:30158362 found that 63% of cases showed hyperandrogenism and impaired fertility (ambiguous genitalia, hirsutism and oligomenorrhoea in females; precocious puberty and oligospermia in males). 50% cases showed hyperaldosteronism, with or without hypertensionand/or hypokalemia.

There are also 4 biallelic cases (PMID:19933394; 7683692; 11932321; 31145715).

There is enough evidence to support a gene-disease association. Therefore this gene should be rated Green at the next review.
Disorders of sex development v2.39 NR3C1 Ivone Leong Gene: nr3c1 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.38 NR3C1 Ivone Leong Tag Q2_21_rating tag was added to gene: NR3C1.
Disorders of sex development v2.38 NR3C1 Ivone Leong Phenotypes for gene: NR3C1 were changed from Glucocorticoid resistance (MIM#615962) to Glucocorticoid resistance, OMIM:615962
Disorders of sex development v2.37 MYRF Ivone Leong Classified gene: MYRF as Amber List (moderate evidence)
Disorders of sex development v2.37 MYRF Ivone Leong Added comment: Comment on list classification: This gene is associated with a phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association and this gene should be promoted to Green at the next review.
Disorders of sex development v2.37 MYRF Ivone Leong Gene: myrf has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.36 MYRF Ivone Leong Tag Q2_21_rating tag was added to gene: MYRF.
Disorders of sex development v2.36 MYRF Ivone Leong Phenotypes for gene: MYRF were changed from Cardiac-urogenital syndrome; gonadal hypoplasia; Müllerian duct hypoplasia to Cardiac-urogenital syndrome, OMIM:618280; gonadal hypoplasia; Mullerian duct hypoplasia
Disorders of sex development v2.35 ESR2 Ivone Leong Classified gene: ESR2 as Amber List (moderate evidence)
Disorders of sex development v2.35 ESR2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is currently not enough evidence to support a gene-disease association. Therefore, this gene has been given an Amber rating.
Disorders of sex development v2.35 ESR2 Ivone Leong Gene: esr2 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.34 ESR2 Ivone Leong Tag watchlist tag was added to gene: ESR2.
Disorders of sex development v2.34 ESR2 Ivone Leong Phenotypes for gene: ESR2 were changed from 46,XY disorder of sex development, MONDO:0020040; Ovarian dysgenesis 8, OMIM:618187 to 46,XY disorder of sex development, MONDO:0020040; ?Ovarian dysgenesis 8, OMIM:618187
Disorders of sex development v2.33 ESR2 Ivone Leong Phenotypes for gene: ESR2 were changed from 46,XY disorder of sex development; Ovarian dysgenesis 8, MIM# 618187 to 46,XY disorder of sex development, MONDO:0020040; Ovarian dysgenesis 8, OMIM:618187
Disorders of sex development v2.32 FGFR2 Ivone Leong Publications for gene: FGFR2 were set to 26362256; 18155190
Disorders of sex development v2.31 FGFR2 Ivone Leong Publications for gene: FGFR2 were set to 26362256; 18155190; 2238701
Disorders of sex development v2.30 FGFR2 Ivone Leong Publications for gene: FGFR2 were set to 26362256; 18155190
Disorders of sex development v2.29 FGFR2 Ivone Leong Phenotypes for gene: FGFR2 were changed from LADD syndrome 149730; Bent bone dysplasia syndrome 614592 to LADD syndrome, OMIM:149730; Bent bone dysplasia syndrome, OMIM:614592
Disorders of sex development v2.28 GATA4 Ivone Leong Tag Q2_21_rating tag was added to gene: GATA4.
Disorders of sex development v2.28 GATA4 Ivone Leong Classified gene: GATA4 as Amber List (moderate evidence)
Disorders of sex development v2.28 GATA4 Ivone Leong Added comment: Comment on list classification: This gene is associated with a phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be promoted to Green at the next review.
Disorders of sex development v2.28 GATA4 Ivone Leong Gene: gata4 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.27 GATA4 Ivone Leong Publications for gene: GATA4 were set to 21220346
Disorders of sex development v2.26 GATA4 Ivone Leong Phenotypes for gene: GATA4 were changed from ?Testicular anomalies with or without congenital heart disease 615542 to ?Testicular anomalies with or without congenital heart disease, OMIM:615542
Disorders of sex development v2.25 HOXA13 Ivone Leong Classified gene: HOXA13 as Amber List (moderate evidence)
Disorders of sex development v2.25 HOXA13 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Disorders of sex development v2.25 HOXA13 Ivone Leong Gene: hoxa13 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.24 HOXA13 Ivone Leong Tag Q2_21_rating tag was added to gene: HOXA13.
Disorders of sex development v2.24 HOXA13 Ivone Leong Phenotypes for gene: HOXA13 were changed from Hand-foot-uterus syndrome, MIM# 140000 to Hand-foot-uterus syndrome, OMIM:140000
Disorders of sex development v2.23 PAX8 Ivone Leong Classified gene: PAX8 as Amber List (moderate evidence)
Disorders of sex development v2.23 PAX8 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. This gene has been given an Amber rating as more evidence is required to support a gene-disease association.
Disorders of sex development v2.23 PAX8 Ivone Leong Gene: pax8 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.22 PAX8 Ivone Leong Tag watchlist tag was added to gene: PAX8.
Disorders of sex development v2.22 PAX8 Ivone Leong Added comment: Comment on publications: PMID: 25484916 describes a case of a patient with MRKH and hypothyroidism with a de novo deletion of 2q13-14.2 region (includes PAX8).

PMID: 31731040 describes a second case of a patient with MRKH and congenital thyroid gland hypoplasia with a de novo interstitial 2q12.1q14.1 deletion (the region includes PAX8).

In both PMID: 25484916 and 31731040, the authors theorise that PAX8 may be responsible.
Disorders of sex development v2.22 PAX8 Ivone Leong Publications for gene: PAX8 were set to 33434492
Disorders of sex development v2.21 PAX8 Ivone Leong Phenotypes for gene: PAX8 were changed from Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), MONDO:0017771
Disorders of sex development v2.20 PBX1 Ivone Leong Phenotypes for gene: PBX1 were changed from 46, XY gonadal dysgenesis to 46, XY gonadal dysgenesis; 46,XY partial gonadal dysgenesis, MONDO:0016674
Disorders of sex development v2.19 PBX1 Ivone Leong Tag watchlist tag was added to gene: PBX1.
Disorders of sex development v2.19 PBX1 Ivone Leong Classified gene: PBX1 as Amber List (moderate evidence)
Disorders of sex development v2.19 PBX1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. As there is currently not enough evidence to support a gene-disease association, this gene has been given an Amber rating.
Disorders of sex development v2.19 PBX1 Ivone Leong Gene: pbx1 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.18 NR2F2 Ivone Leong Tag Q2_21_rating tag was added to gene: NR2F2.
Disorders of sex development v2.18 NR2F2 Ivone Leong Classified gene: NR2F2 as Amber List (moderate evidence)
Disorders of sex development v2.18 NR2F2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. Therefore this gene should be Green at the next review.
Disorders of sex development v2.18 NR2F2 Ivone Leong Gene: nr2f2 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.17 NR2F2 Ivone Leong Phenotypes for gene: NR2F2 were changed from 46,XX disorder of sex development (DSD) and congenital heart defects to 46,XX sex reversal 5, OMIM:618901; 46,XX sex reversal 5, MONDO:0030049
Disorders of sex development v2.16 PAX8 Zornitza Stark gene: PAX8 was added
gene: PAX8 was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: PAX8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAX8 were set to 33434492
Phenotypes for gene: PAX8 were set to Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)
Review for gene: PAX8 was set to AMBER
Added comment: Variants in this gene are associated with congenital hypothyroidism.

5 individuals identified in large cohorts with MRKHS and likely deleterious variants in PAX8. At least one of the individuals had congenital hypothyroidism together with features of MRKHS, suggesting this is phenotype expansion. Amber rating suggested due to limited case-level data.
Sources: Literature
Disorders of sex development v2.16 ISCA-46302-Gain Catherine Snow Tag for-review tag was added to Region: ISCA-46302-Gain.
Disorders of sex development v2.16 ISCA-46302-Gain Catherine Snow Classified Region: ISCA-46302-Gain as Amber List (moderate evidence)
Disorders of sex development v2.16 ISCA-46302-Gain Catherine Snow Added comment: Comment on list classification: Addition of region inline with ClinGen regions classifications. Reviewed by GEL clinical team for panel phenotype, NR0B1 green on panel so CNV should be added too and phenotype of gonadal dysgenesis relevant to this panel.
Disorders of sex development v2.16 ISCA-46302-Gain Catherine Snow Region: isca-46302-gain has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.15 ISCA-46302-Gain Catherine Snow Region: ISCA-46302-Gain was added
Region: ISCA-46302-Gain was added to Disorders of sex development. Sources: ClinGen
Mode of inheritance for Region: ISCA-46302-Gain was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for Region: ISCA-46302-Gain were set to 22518125; 17504899; 20685758
Phenotypes for Region: ISCA-46302-Gain were set to gonadal dysgenesis
Review for Region: ISCA-46302-Gain was set to AMBER
Added comment: Sources: ClinGen
Disorders of sex development v2.14 TSPYL1 Eleanor Williams Classified gene: TSPYL1 as Amber List (moderate evidence)
Disorders of sex development v2.14 TSPYL1 Eleanor Williams Added comment: Comment on list classification: Leaving rating as amber, but there are 3 cases now reported and so this gene should be reviewed at the next GMS update.
Disorders of sex development v2.14 TSPYL1 Eleanor Williams Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.13 TSPYL1 Eleanor Williams Phenotypes for gene: TSPYL1 were changed from Sudden infant death with dysgenesis of the testes syndrome 608800 to Sudden infant death with dysgenesis of the testes syndrome OMIM:608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124
Disorders of sex development v2.12 TSPYL1 Eleanor Williams Publications for gene: TSPYL1 were set to 15273283; 22137496; 19463995
Disorders of sex development v2.11 TSPYL1 Eleanor Williams Tag for-review tag was added to gene: TSPYL1.
Disorders of sex development v2.11 TSPYL1 Eleanor Williams reviewed gene: TSPYL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 32885560, 33075815; Phenotypes: Sudden infant death with dysgenesis of the testes syndrome OMIM:608800, sudden infant death-dysgenesis of the testes syndrome MONDO:0012124; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of sex development v2.11 TCF12 Arina Puzriakova changed review comment from: Comment on list classification: Variants in TCF12 typically cause craniosynostosis, while evidence for an association with Kallmann Syndrome is currently based on a single study, and therefore warrants further investigation. Furthermore, the presence of incomplete penetrance must be considered.

Additional cases would help validate the pathogenicity of TCF12 variants in aberrant GnRH axis development.

Therefore, rating Amber in anticipation of additional publications/clinical evidence (added to watchlist).; to: Comment on list classification: Variants in TCF12 typically cause craniosynostosis, while evidence for an association with Kallmann Syndrome is currently based on a single study, and therefore warrants further investigation. Furthermore, the presence of incomplete penetrance must be considered. Additional cases would help validate the pathogenicity of TCF12 variants in aberrant GnRH axis development.

Therefore, rating Amber in anticipation of additional publications/clinical evidence (added to watchlist).
Disorders of sex development v2.11 TCF12 Arina Puzriakova Tag watchlist tag was added to gene: TCF12.
Disorders of sex development v2.11 TCF12 Arina Puzriakova Classified gene: TCF12 as Amber List (moderate evidence)
Disorders of sex development v2.11 TCF12 Arina Puzriakova Added comment: Comment on list classification: Variants in TCF12 typically cause craniosynostosis, while evidence for an association with Kallmann Syndrome is currently based on a single study, and therefore warrants further investigation. Furthermore, the presence of incomplete penetrance must be considered.

Additional cases would help validate the pathogenicity of TCF12 variants in aberrant GnRH axis development.

Therefore, rating Amber in anticipation of additional publications/clinical evidence (added to watchlist).
Disorders of sex development v2.11 TCF12 Arina Puzriakova Gene: tcf12 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.10 TCF12 Arina Puzriakova gene: TCF12 was added
gene: TCF12 was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: TCF12 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TCF12 were set to 32620954
Phenotypes for gene: TCF12 were set to Kallmann syndrome
Review for gene: TCF12 was set to AMBER
Added comment: Note monoallelic variants in this gene are a well-established cause of craniosynostosis.
--------------------------------------------------------------------------------------------------------------------

- PMID: 32620954 (2020) - 13 unrelated kindreds (11 de novo, 1 AD and 1 AR) comprising 14 affected individuals with an anosmic form of isolated GnRH deficiency (IGD) (Kallman syndrome) due to different LoF variants in TCF12.

Clinical manifestation included anosmia and pubertal failure (with reproductive phenotypes such as micropenis, bilateral cryptorchidism, hypospadias). Two unrelated individuals within the cohort additionally exhibited craniosynostosis, and a further two pedigrees had a family history of craniosynostosis (that did not affect the index cases). Multiplex cases typically presented incomplete penetrance.

Loss of tcf12 in a mutant zebrafish model perturbed GnRH neuronal patterning, with concomitant expression attenuation of tcf3a/b and stub1 (latter mutated in other syndromic forms of IGD). Furthermore, restored STUB1 expression rescued loss of tcf12 in vivo.
Sources: Literature
Disorders of sex development v2.9 DHX37 Arina Puzriakova Tag for-review tag was added to gene: DHX37.
Disorders of sex development v2.9 DHX37 Arina Puzriakova Publications for gene: DHX37 were set to 31337883; 31745530
Disorders of sex development v2.8 DHX37 Arina Puzriakova Phenotypes for gene: DHX37 were changed from 46,XY gonadal dysgenesis; testicular regression syndrome (TRS) to 46, XY sex reversal 11, 273250
Disorders of sex development v2.7 DHX37 Arina Puzriakova Classified gene: DHX37 as Amber List (moderate evidence)
Disorders of sex development v2.7 DHX37 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review.
Disorders of sex development v2.7 DHX37 Arina Puzriakova Gene: dhx37 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.6 DHX37 Arina Puzriakova reviewed gene: DHX37: Rating: GREEN; Mode of pathogenicity: None; Publications: 31287541, 31745530, 31337883; Phenotypes: 46, XY sex reversal 11, 273250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Disorders of sex development v2.6 PPP1R12A Arina Puzriakova Classified gene: PPP1R12A as Amber List (moderate evidence)
Disorders of sex development v2.6 PPP1R12A Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - at least 7 unrelated cases with significant genitourinary malformations.
Disorders of sex development v2.6 PPP1R12A Arina Puzriakova Gene: ppp1r12a has been classified as Amber List (Moderate Evidence).
Disorders of sex development v2.5 PPP1R12A Arina Puzriakova gene: PPP1R12A was added
gene: PPP1R12A was added to Disorders of sex development. Sources: Literature
for-review tags were added to gene: PPP1R12A.
Mode of inheritance for gene: PPP1R12A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PPP1R12A were set to 31883643
Phenotypes for gene: PPP1R12A were set to Genitourinary and/or/brain malformation syndrome, 618820
Review for gene: PPP1R12A was set to GREEN
Added comment: Associated with phenotype in OMIM, and a probable gene for PPP1R12A-related Holoprosencephaly Spectrum and Urogenital Malformations in G2P.

PMID: 31883643 (2020) - Screening cohorts of patients with holoprosencephaly and patients with disorders of sex development revealed 12 unrelated individuals with de novo LoF variants in the PPP1R12A gene. Variants were associated with a broad spectrum of manifestations, and a clear genotype-phenotype correlation was not observed - most commonly presentation included either malformations of the brain or the genitourinary tract (two individuals exhibited both brain and genitourinary anomalies). Out of the 12 patients, 4 were XY females and 3 were XY males with significant anomalies.
Sources: Literature
Disorders of sex development v2.4 HOXA13 Zornitza Stark gene: HOXA13 was added
gene: HOXA13 was added to Disorders of sex development. Sources: Expert list
Mode of inheritance for gene: HOXA13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HOXA13 were set to 10839976; 9020844
Phenotypes for gene: HOXA13 were set to Hand-foot-uterus syndrome, MIM# 140000
Review for gene: HOXA13 was set to GREEN
gene: HOXA13 was marked as current diagnostic
Added comment: Hypospadias/bifid scrotum in males, Mullerian duct fusion defects in females (double uterus, double cervix, longitudinal vaginal septum).
Sources: Expert list
Disorders of sex development v2.4 GATA4 Zornitza Stark reviewed gene: GATA4: Rating: GREEN; Mode of pathogenicity: None; Publications: 21220346, 31962012; Phenotypes: Testicular anomalies with or without congenital heart disease, MIM#615542; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Disorders of sex development v2.4 FGFR2 Zornitza Stark gene: FGFR2 was added
gene: FGFR2 was added to Disorders of sex development. Sources: Expert list
Mode of inheritance for gene: FGFR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR2 were set to 26362256; 18155190
Phenotypes for gene: FGFR2 were set to LADD syndrome 149730; Bent bone dysplasia syndrome 614592
Review for gene: FGFR2 was set to GREEN
Added comment: PMID: 26362256 - 1 individual with craniosynostosis and XY sex reversal and a missense variant. Phenotype recapitulated using mouse model, concludes a LOF mechanism.

PMID: 18155190 - partial null mutant mouse model shows XY sex reversal

PMID: 2238701 - 4 fetuses with de novo mutations and a skeletal disorder 3/4 had clitoromegaly, last fetus only had radiograph available. p.(Met391Arg) is recurring, variants are supported by functional studies showing protein mislocalization

Mutations reported for all other FGFR2-related conditions have a GOF mechanism
Sources: Expert list
Disorders of sex development v2.4 ESR2 Zornitza Stark gene: ESR2 was added
gene: ESR2 was added to Disorders of sex development. Sources: Expert list
Mode of inheritance for gene: ESR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ESR2 were set to 29261182; 9861029; 30113650
Phenotypes for gene: ESR2 were set to 46,XY disorder of sex development; Ovarian dysgenesis 8, MIM# 618187
Review for gene: ESR2 was set to AMBER
Added comment: A homozygous indel (Asn181del) was identified in a syndromic case with 46,XY DSD, and 2 heterozygous missense variants were identified in 2 non-syndromic cases with 46,XY DSD. Asn181del and Leu426Arg were found to have significantly increased transcriptional activation in in vitro luciferase assays. Esrb null male mice showed no overt abnormalities and reproduced normally. Older mutant males displayed signs of prostate and bladder hyperplasia.
A further individual reported with 46,XX karyotype and ovarian dysgenesis (PMID: 30113650)
Sources: Expert list
Disorders of sex development v2.4 MYRF Zornitza Stark reviewed gene: MYRF: Rating: GREEN; Mode of pathogenicity: None; Publications: 30985895, 29446546, 31069960, 30070761, 30532227; Phenotypes: Cardiac-urogenital syndrome, gonadal hypoplasia, Müllerian duct hypoplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Disorders of sex development v2.4 NR3C1 Zornitza Stark gene: NR3C1 was added
gene: NR3C1 was added to Disorders of sex development. Sources: Expert list
Mode of inheritance for gene: NR3C1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR3C1 were set to 30158362
Phenotypes for gene: NR3C1 were set to Glucocorticoid resistance (MIM#615962)
Review for gene: NR3C1 was set to GREEN
gene: NR3C1 was marked as current diagnostic
Added comment: Features include hyperandrogenism with features of ambiguous genitalia, precocious puberty, advanced bone age, infertility, amenorrhea, clitoromegaly, oligospermia. PMID: 30158362: Review of >5 patients reported with the associated phenotype.
Sources: Expert list
Disorders of sex development v2.4 PBX1 Zornitza Stark gene: PBX1 was added
gene: PBX1 was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: PBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PBX1 were set to 31302614; 31058389
Phenotypes for gene: PBX1 were set to 46, XY gonadal dysgenesis
Review for gene: PBX1 was set to AMBER
Added comment: Two individuals reported with mono allelic variants in this gene and 46,XY gonadal dysgenesis.
Sources: Literature
Disorders of sex development v2.4 NR2F2 Zornitza Stark edited their review of gene: NR2F2: Set current diagnostic: yes
Disorders of sex development v2.4 NR2F2 Zornitza Stark gene: NR2F2 was added
gene: NR2F2 was added to Disorders of sex development. Sources: Expert list
Mode of inheritance for gene: NR2F2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F2 were set to 29478779; 31687637
Phenotypes for gene: NR2F2 were set to 46,XX disorder of sex development (DSD) and congenital heart defects
Review for gene: NR2F2 was set to GREEN
Added comment: Four unrelated individuals reported. Note two had the same 7bp deletion, c.97_103delCCGCCCG, NM_021005.3, and the third individual had an adjacent deletion, c.103_109delGGCGCCC, NM_021005.3. All three were of very different ancestries, making founder effect unlikely. Fourth individual had a larger deletion encompassing this gene. Gene is also linked with isolated CHD (Congenital heart defects, multiple types, 4, MIM# 615779)
Sources: Expert list
Disorders of sex development v2.4 DHX37 Zornitza Stark gene: DHX37 was added
gene: DHX37 was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: DHX37 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX37 were set to 31337883; 31745530
Phenotypes for gene: DHX37 were set to 46,XY gonadal dysgenesis; testicular regression syndrome (TRS)
Review for gene: DHX37 was set to GREEN
gene: DHX37 was marked as current diagnostic
Added comment: Seventeen individuals reported in two studies.
Sources: Literature
Disorders of sex development v2.3 Catherine Snow Panel version has been signed off
Disorders of sex development v2.1 MYRF Ivone Leong Classified gene: MYRF as Red List (low evidence)
Disorders of sex development v2.1 MYRF Ivone Leong Added comment: Comment on list classification: New gene added by reviewer. I have given this gene a Red rating as this was added after the panel has been signed-off by the GMS specialist group.
Disorders of sex development v2.1 MYRF Ivone Leong Gene: myrf has been classified as Red List (Low Evidence).
Disorders of sex development v2.0 MYRF Martina Owens gene: MYRF was added
gene: MYRF was added to Disorders of sex development. Sources: Literature
Mode of inheritance for gene: MYRF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYRF were set to 30985895; 29446546; 31069960; 30070761; 30532227
Phenotypes for gene: MYRF were set to Cardiac-urogenital syndrome; gonadal hypoplasia; Müllerian duct hypoplasia
Penetrance for gene: MYRF were set to unknown
Review for gene: MYRF was set to AMBER
Added comment: Hamanaka et al 2019 (PMID:30985895): enrichment study plus an independent cohort. Identified 3 de novo MYRF truncating variants in 4 DSD cases (3 families - 2 cases were monozygotic twins) and a de novo missense variant in 1 DSD case. Pinz et al 2018 (PMID: 29446546) reported de novo truncating MYRF variants in 2 male cases with genitourinary anomalies with congenital heart defects. Chitayat et al 2018 (PMID: 30070761) reported truncating variant in a patient with ambiguous genitalia and hypoplastic left heart syndrome. Qi et al 2018 (PMID: 30532227) reported 7 de novo patients with DSD, congenital heart defects and congenital diaphragmatic hernia. Rossetti et al 2019 (PMID: 31069960) reported above patients and 2 further patients with genitourinary anomalies and congenital diaphragmatic hernia.
Sources: Literature
Disorders of sex development v2.0 Ivone Leong promoted panel to version 2.0
Disorders of sex development v1.37 Ivone Leong List of related panels changed from to R146
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Disorders of sex development v1.36 ZFPM2 Ivone Leong Classified gene: ZFPM2 as Amber List (moderate evidence)
Disorders of sex development v1.36 ZFPM2 Ivone Leong Added comment: Comment on list classification: Demoted from green to amber based on the evidence provided by Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust).
Disorders of sex development v1.36 ZFPM2 Ivone Leong Gene: zfpm2 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v1.35 ZFPM2 Martina Owens reviewed gene: ZFPM2: Rating: AMBER; Mode of pathogenicity: None; Publications: 24549039, 27899157, 12223418; Phenotypes: 46XY sex reversal 9 616067; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Disorders of sex development v1.34 TSPYL1 Ivone Leong Classified gene: TSPYL1 as Amber List (moderate evidence)
Disorders of sex development v1.34 TSPYL1 Ivone Leong Added comment: Comment on list classification: Promoted from red to amber. TSPYL1 is associated with a phenotype in OMIM but not Gene2Phenotype. As there are only 2 unrelated cases with different variants in the gene, it was decided that there is currently not enough evidence to promote to green status. There was agreement to promote this gene to amber by experts in GMS Endocrinology Specialist Test Group. Until further evidence is available, TSPYL1 will be promoted to amber.
Disorders of sex development v1.34 TSPYL1 Ivone Leong Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Disorders of sex development v1.33 SGPL1 Ivone Leong Classified gene: SGPL1 as Green List (high evidence)
Disorders of sex development v1.33 SGPL1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. There was agreement to promote to green because experts in paediatric endocrinology agreed that ambiguous genitalia may be the presenting feature in some cases, and an early diagnosis may significantly reduce the chance of adverse clinical outcomes
Disorders of sex development v1.33 SGPL1 Ivone Leong Gene: sgpl1 has been classified as Green List (High Evidence).
Disorders of sex development v1.32 CYP21A2 Ivone Leong Deleted their comment
Disorders of sex development v1.32 ISCA-37401-Loss Ivone Leong reviewed Region: ISCA-37401-Loss: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Disorders of sex development v1.32 ZFPM2 Ivone Leong reviewed gene: ZFPM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 WT1 Ivone Leong reviewed gene: WT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 TOE1 Ivone Leong reviewed gene: TOE1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 STAR Ivone Leong reviewed gene: STAR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 SRY Ivone Leong reviewed gene: SRY: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 SRD5A2 Ivone Leong reviewed gene: SRD5A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 SOX9 Ivone Leong reviewed gene: SOX9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 SOX10 Ivone Leong reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 SAMD9 Ivone Leong reviewed gene: SAMD9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 RSPO1 Ivone Leong reviewed gene: RSPO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 RPL10 Ivone Leong reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 POR Ivone Leong reviewed gene: POR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 NR5A1 Ivone Leong reviewed gene: NR5A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 NR0B1 Ivone Leong reviewed gene: NR0B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 MAP3K1 Ivone Leong reviewed gene: MAP3K1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 MAMLD1 Ivone Leong reviewed gene: MAMLD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 LHCGR Ivone Leong reviewed gene: LHCGR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 HSD3B2 Ivone Leong reviewed gene: HSD3B2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 HSD17B3 Ivone Leong reviewed gene: HSD17B3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 DHH Ivone Leong reviewed gene: DHH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 DHCR7 Ivone Leong reviewed gene: DHCR7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CYP21A2 Ivone Leong reviewed gene: CYP21A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CYP19A1 Ivone Leong reviewed gene: CYP19A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CYP17A1 Ivone Leong reviewed gene: CYP17A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CYP11B1 Ivone Leong reviewed gene: CYP11B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CYP11A1 Ivone Leong reviewed gene: CYP11A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CYB5A Ivone Leong reviewed gene: CYB5A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CUL4B Ivone Leong reviewed gene: CUL4B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CHD7 Ivone Leong reviewed gene: CHD7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 CDKN1C Ivone Leong reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 ATRX Ivone Leong reviewed gene: ATRX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 ARX Ivone Leong reviewed gene: ARX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 AR Ivone Leong reviewed gene: AR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Disorders of sex development v1.32 AMHR2 Ivone Leong edited their review of gene: AMHR2: Added comment: As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.; Changed rating: GREEN
Disorders of sex development v1.32 AMH Ivone Leong edited their review of gene: AMH: Added comment: As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.; Changed rating: GREEN
Disorders of sex development v1.31 TSPYL1 Stephanie Allen reviewed gene: TSPYL1: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of sex development v1.31 AMHR2 Ivone Leong Classified gene: AMHR2 as Green List (high evidence)
Disorders of sex development v1.31 AMHR2 Ivone Leong Added comment: Comment on list classification: Promoted from red to green as recommended by Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust). There are >3 unrelated cases of patients with variants in AMHR2 who have Persistent Mullerian duct syndrome, type II (PMID: 28528332).
Disorders of sex development v1.31 AMHR2 Ivone Leong Gene: amhr2 has been classified as Green List (High Evidence).
Disorders of sex development v1.30 AMH Ivone Leong Deleted their comment
Disorders of sex development v1.30 AMH Ivone Leong Classified gene: AMH as Green List (high evidence)
Disorders of sex development v1.30 AMH Ivone Leong Added comment: Comment on list classification: Promoted from red to green as recommended by Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust). There are >3 unrelated cases of patients with variants in AMH who have Persistent Mullerian duct syndrome, type I (PMID: 28528332).
Disorders of sex development v1.30 AMH Ivone Leong Gene: amh has been classified as Green List (High Evidence).
Disorders of sex development v1.29 AMH Ivone Leong Classified gene: AMH as Green List (high evidence)
Disorders of sex development v1.29 AMH Ivone Leong Added comment: Comment on list classification: Promoted from red to green as recommended by Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust). There are >3 unrelated cases of patients with variants in AMH who have Persistent Mullerian duct syndrome, type I (PMID: 28528332).
Disorders of sex development v1.29 AMH Ivone Leong Gene: amh has been classified as Green List (High Evidence).
Disorders of sex development v1.28 AMHR2 Martina Owens reviewed gene: AMHR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28528332; Phenotypes: Persistent Mullerian duct syndrome, type II, 261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of sex development v1.28 AMH Martina Owens reviewed gene: AMH: Rating: GREEN; Mode of pathogenicity: ; Publications: 28528332; Phenotypes: Persistent Mullerian duct syndrome, type I, 261550; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Disorders of sex development v1.27 AMHR2 Ivone Leong gene: AMHR2 was added
gene: AMHR2 was added to Disorders of sex development. Sources: NHS GMS
Mode of inheritance for gene: AMHR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMHR2 were set to 28528332
Phenotypes for gene: AMHR2 were set to Persistent Mullerian duct syndrome, type II, 261550
Disorders of sex development v1.27 AMH Ivone Leong gene: AMH was added
gene: AMH was added to Disorders of sex development. Sources: NHS GMS
Mode of inheritance for gene: AMH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMH were set to 28528332
Phenotypes for gene: AMH were set to Persistent Mullerian duct syndrome, type I, 261550
Disorders of sex development v1.25 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual
Disorders of sex development v1.24 ISCA-37401-Loss Louise Daugherty Region: ISCA-37401-Loss was added
Region: ISCA-37401-Loss was added to Disorders of sex development. Sources: ClinGen,Expert Review Green
Mode of inheritance for Region: ISCA-37401-Loss was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for Region: ISCA-37401-Loss were set to Wilms tumor, aniridia, genitourinary anomalies and mental retardation syndrome; 194072
Disorders of sex development SGPL1 Sarah Leigh classified SGPL1 as amber
Disorders of sex development SGPL1 Sarah Leigh added SGPL1 to panel
Disorders of sex development SGPL1 Sarah Leigh reviewed SGPL1
Disorders of sex development RPL10 Sarah Leigh classified RPL10 as green
Disorders of sex development RPL10 Sarah Leigh added RPL10 to panel
Disorders of sex development RPL10 Sarah Leigh reviewed RPL10
Disorders of sex development ERAL1 Sarah Leigh added ERAL1 to panel
Disorders of sex development ERAL1 Sarah Leigh reviewed ERAL1
Disorders of sex development MCM5 Sarah Leigh added MCM5 to panel
Disorders of sex development MCM5 Sarah Leigh reviewed MCM5
Disorders of sex development TOE1 Helen Brittain marked TOE1 as ready
Disorders of sex development TOE1 Helen Brittain classified TOE1 as green
Disorders of sex development TOE1 Helen Brittain added TOE1 to panel
Disorders of sex development TOE1 Helen Brittain reviewed TOE1
Disorders of sex development SAMD9 Helen Brittain marked SAMD9 as ready
Disorders of sex development SAMD9 Helen Brittain classified SAMD9 as green
Disorders of sex development SAMD9 Helen Brittain added SAMD9 to panel
Disorders of sex development SAMD9 Helen Brittain reviewed SAMD9
Disorders of sex development ATRX Sarah Leigh marked ATRX as ready
Disorders of sex development ATRX Sarah Leigh classified ATRX as green
Disorders of sex development ATRX Sarah Leigh commented on ATRX
Disorders of sex development ATRX emma baple added ATRX to panel
Disorders of sex development ATRX emma baple reviewed ATRX
Disorders of sex development SRY Ellen McDonagh commented on SRY
Disorders of sex development WT1 Ellen McDonagh commented on WT1
Disorders of sex development Sarah Leigh promoted panel to version 1
Disorders of sex development NR0B1 Sarah Leigh marked NR0B1 as ready
Disorders of sex development INPP5E Sarah Leigh marked INPP5E as ready
Disorders of sex development INPP5E Sarah Leigh classified INPP5E as red
Disorders of sex development CUL4B Sarah Leigh marked CUL4B as ready
Disorders of sex development CUL4B Sarah Leigh commented on CUL4B
Disorders of sex development GLI2 Sarah Leigh marked GLI2 as ready
Disorders of sex development GLI2 Sarah Leigh classified GLI2 as red
Disorders of sex development CHD7 Sarah Leigh marked CHD7 as ready
Disorders of sex development CHD7 Sarah Leigh commented on CHD7
Disorders of sex development TSPYL1 Sarah Leigh marked TSPYL1 as ready
Disorders of sex development TSPYL1 Sarah Leigh classified TSPYL1 as red
Disorders of sex development TSPYL1 Sarah Leigh classified TSPYL1 as red
Disorders of sex development ZFPM2 Sarah Leigh marked ZFPM2 as ready
Disorders of sex development ZFPM2 Sarah Leigh classified ZFPM2 as green
Disorders of sex development ZFPM2 Sarah Leigh commented on ZFPM2
Disorders of sex development ZFPM2 Sarah Leigh classified ZFPM2 as green
Disorders of sex development TSPYL1 Sarah Leigh marked TSPYL1 as ready
Disorders of sex development TSPYL1 Sarah Leigh classified TSPYL1 as amber
Disorders of sex development TSPYL1 Sarah Leigh commented on TSPYL1
Disorders of sex development TSPYL1 Sarah Leigh classified TSPYL1 as green
Disorders of sex development TAF4B Sarah Leigh marked TAF4B as ready
Disorders of sex development MAP3K1 Sarah Leigh marked MAP3K1 as ready
Disorders of sex development MAP3K1 Sarah Leigh classified MAP3K1 as green
Disorders of sex development MAP3K1 Sarah Leigh commented on MAP3K1
Disorders of sex development HSD17B2 Sarah Leigh marked HSD17B2 as ready
Disorders of sex development HSD17B2 Sarah Leigh commented on HSD17B2
Disorders of sex development HHAT Sarah Leigh marked HHAT as ready
Disorders of sex development HHAT Sarah Leigh commented on HHAT
Disorders of sex development DMRT1 Sarah Leigh marked DMRT1 as ready
Disorders of sex development DMRT1 Sarah Leigh commented on DMRT1
Disorders of sex development DGKQ Sarah Leigh marked DGKQ as ready
Disorders of sex development DGKQ Sarah Leigh commented on DGKQ
Disorders of sex development TAF4B Sarah Leigh reviewed TAF4B
Disorders of sex development SOX10 Sarah Leigh edited their review of SOX10
Disorders of sex development SOX10 Sarah Leigh commented on SOX10
Disorders of sex development SEMA3E Sarah Leigh commented on SEMA3E
Disorders of sex development INPP5E Sarah Leigh edited their review of INPP5E
Disorders of sex development INPP5E Sarah Leigh commented on INPP5E
Disorders of sex development GLI2 Sarah Leigh commented on GLI2
Disorders of sex development RSPO1 Sarah Leigh classified RSPO1 as green
Disorders of sex development NR0B1 Sarah Leigh commented on NR0B1
Disorders of sex development PAX6 Sarah Leigh marked PAX6 as ready
Disorders of sex development PAX6 Sarah Leigh classified PAX6 as red
Disorders of sex development PAX6 Sarah Leigh commented on PAX6
Disorders of sex development CDKN1C Sarah Leigh marked CDKN1C as ready
Disorders of sex development CDKN1C Sarah Leigh commented on CDKN1C
Disorders of sex development ARX Sarah Leigh marked ARX as ready
Disorders of sex development ARX Sarah Leigh commented on ARX
Disorders of sex development CYB5A Sarah Leigh marked CYB5A as ready
Disorders of sex development CYB5A Sarah Leigh commented on CYB5A
Disorders of sex development CYB5A Sarah Leigh classified CYB5A as green
Disorders of sex development AKR1C2 Sarah Leigh marked AKR1C2 as ready
Disorders of sex development AKR1C2 Sarah Leigh commented on AKR1C2
Disorders of sex development SRD5A2 Sarah Leigh marked SRD5A2 as ready
Disorders of sex development SRD5A2 Sarah Leigh classified SRD5A2 as green
Disorders of sex development SRD5A2 Sarah Leigh commented on SRD5A2
Disorders of sex development RSPO1 Sarah Leigh marked RSPO1 as ready
Disorders of sex development RSPO1 Sarah Leigh commented on RSPO1
Disorders of sex development MAMLD1 Sarah Leigh classified MAMLD1 as green
Disorders of sex development MAMLD1 Sarah Leigh marked MAMLD1 as ready
Disorders of sex development MAMLD1 Sarah Leigh commented on MAMLD1
Disorders of sex development GATA4 Sarah Leigh classified GATA4 as red
Disorders of sex development GATA4 Sarah Leigh marked GATA4 as ready
Disorders of sex development DHH Sarah Leigh marked DHH as ready
Disorders of sex development DHH Sarah Leigh commented on DHH
Disorders of sex development CYP21A2 Sarah Leigh marked CYP21A2 as ready
Disorders of sex development CYP21A2 Sarah Leigh commented on CYP21A2
Disorders of sex development CBX2 Sarah Leigh marked CBX2 as ready
Disorders of sex development CBX2 Sarah Leigh commented on CBX2
Disorders of sex development CBX2 Sarah Leigh classified CBX2 as red
Disorders of sex development ATP6V0A4 Sarah Leigh marked ATP6V0A4 as ready
Disorders of sex development ATP6V0A4 Sarah Leigh classified ATP6V0A4 as red
Disorders of sex development ATP6V0A4 Sarah Leigh commented on ATP6V0A4
Disorders of sex development AR Sarah Leigh marked AR as ready
Disorders of sex development AR Sarah Leigh classified AR as green
Disorders of sex development AR Sarah Leigh commented on AR
Disorders of sex development STAR Sarah Leigh marked STAR as ready
Disorders of sex development STAR Sarah Leigh commented on STAR
Disorders of sex development WT1 Sarah Leigh marked WT1 as ready
Disorders of sex development WT1 Sarah Leigh commented on WT1
Disorders of sex development SRY Sarah Leigh marked SRY as ready
Disorders of sex development SRY Sarah Leigh commented on SRY
Disorders of sex development SOX9 Sarah Leigh marked SOX9 as ready
Disorders of sex development SOX9 Sarah Leigh commented on SOX9
Disorders of sex development POR Sarah Leigh marked POR as ready
Disorders of sex development POR Sarah Leigh commented on POR
Disorders of sex development NR5A1 Sarah Leigh marked NR5A1 as ready
Disorders of sex development NR5A1 Sarah Leigh commented on NR5A1
Disorders of sex development LHCGR Sarah Leigh marked LHCGR as ready
Disorders of sex development LHCGR Sarah Leigh commented on LHCGR
Disorders of sex development HSD3B2 Sarah Leigh marked HSD3B2 as ready
Disorders of sex development HSD3B2 Sarah Leigh commented on HSD3B2
Disorders of sex development HSD17B3 Sarah Leigh marked HSD17B3 as ready
Disorders of sex development HSD17B3 Sarah Leigh commented on HSD17B3
Disorders of sex development DHCR7 Sarah Leigh marked DHCR7 as ready
Disorders of sex development DHCR7 Sarah Leigh commented on DHCR7
Disorders of sex development CYP19A1 Sarah Leigh marked CYP19A1 as ready
Disorders of sex development CYP19A1 Sarah Leigh commented on CYP19A1
Disorders of sex development CYP17A1 Sarah Leigh marked CYP17A1 as ready
Disorders of sex development CYP17A1 Sarah Leigh commented on CYP17A1
Disorders of sex development CYP11B1 Sarah Leigh marked CYP11B1 as ready
Disorders of sex development CYP11B1 Sarah Leigh commented on CYP11B1
Disorders of sex development CYP11A1 Sarah Leigh marked CYP11A1 as ready
Disorders of sex development CYP11A1 Sarah Leigh commented on CYP11A1