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| Differences in sex development v4.27 | DMRT1 |
Ida Ertmanska changed review comment from: PMID: 36110220 Zidoune H, et al., 2022 Large study of developmental disorders cohort from North Africa. See suppl material for case details. P_73 - 29 days old male, het for de novo variant NM_021951.3(DMRT1):c.149G>C (p.Ser50Thr); phenotype: Genital bud, preputial orifice and perineal orifice, bifid labioscrotal folds, BC, NPG. Patient was also hemizygous for MAMLD1:NM_005491:c.C2075T:p.A692V - MAMLD1 is associated with Hypospadias 2, X-linked, OMIM:300758. Difficult to decouple the effect of each variant. PMID: 33057194 Kaplanis et al., 2020 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: P_19455: het for NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) P_24289: het for NM_021951.3(DMRT1):c.962C>A (p.Ala321Glu) These variants are not reported in gnomAD v4.1.1. PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026).; to: PMID: 36110220 Zidoune H, et al., 2022 Large study of developmental disorders cohort from North Africa. See suppl material for case details. P_73 - 29 days old male, het for de novo variant NM_021951.3(DMRT1):c.149G>C (p.Ser50Thr); phenotype: Genital bud, preputial orifice and perineal orifice, bifid labioscrotal folds, BC, NPG. Patient was also hemizygous for MAMLD1:NM_005491:c.C2075T:p.A692V - MAMLD1 is associated with Hypospadias 2, X-linked, OMIM:300758. Difficult to decouple the effect of each variant. PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with 46,XY karyotype and variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026). |
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| Differences in sex development v4.24 | DMRT1 |
Ida Ertmanska changed review comment from: PMID: 36110220 Zidoune H, et al., 2022 P_73 - 29 days old male, het for de novo variant NM_021951.3(DMRT1):c.149G>C (p.Ser50Thr); phenotype: Genital bud, preputial orifice and perineal orifice, bifid labioscrotal folds, BC, NPG. Patient was also hemizygous for MAMLD1:NM_005491:c.C2075T:p.A692V - MAMLD1 is associated with Hypospadias 2, X-linked, OMIM:300758. Difficult to decouple the effect of each variant. PMID: 33057194 Kaplanis et al., 2020 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: P_19455: het for NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) P_24289: het for NM_021951.3(DMRT1):c.962C>A (p.Ala321Glu) These variants are not reported in gnomAD v4.1.1. PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026).; to: PMID: 36110220 Zidoune H, et al., 2022 Large study of developmental disorders cohort from North Africa. See suppl material for case details. P_73 - 29 days old male, het for de novo variant NM_021951.3(DMRT1):c.149G>C (p.Ser50Thr); phenotype: Genital bud, preputial orifice and perineal orifice, bifid labioscrotal folds, BC, NPG. Patient was also hemizygous for MAMLD1:NM_005491:c.C2075T:p.A692V - MAMLD1 is associated with Hypospadias 2, X-linked, OMIM:300758. Difficult to decouple the effect of each variant. PMID: 33057194 Kaplanis et al., 2020 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: P_19455: het for NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) P_24289: het for NM_021951.3(DMRT1):c.962C>A (p.Ala321Glu) These variants are not reported in gnomAD v4.1.1. PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026). |
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| Differences in sex development v4.24 | DMRT1 |
Ida Ertmanska changed review comment from: PMID: 33057194 Kaplanis et al., 2020 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: P_19455: het for NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) P_24289: het for NM_021951.3(DMRT1):c.962C>A (p.Ala321Glu) These variants are not reported in gnomAD v4.1.1. PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026).; to: PMID: 36110220 Zidoune H, et al., 2022 P_73 - 29 days old male, het for de novo variant NM_021951.3(DMRT1):c.149G>C (p.Ser50Thr); phenotype: Genital bud, preputial orifice and perineal orifice, bifid labioscrotal folds, BC, NPG. Patient was also hemizygous for MAMLD1:NM_005491:c.C2075T:p.A692V - MAMLD1 is associated with Hypospadias 2, X-linked, OMIM:300758. Difficult to decouple the effect of each variant. PMID: 33057194 Kaplanis et al., 2020 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: P_19455: het for NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) P_24289: het for NM_021951.3(DMRT1):c.962C>A (p.Ala321Glu) These variants are not reported in gnomAD v4.1.1. PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026). |
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| Differences in sex development v4.24 | DMRT1 |
Ida Ertmanska changed review comment from: PMID: 33057194 Kaplanis et al., 2021 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026).; to: PMID: 33057194 Kaplanis et al., 2020 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: P_19455: het for NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) P_24289: het for NM_021951.3(DMRT1):c.962C>A (p.Ala321Glu) These variants are not reported in gnomAD v4.1.1. PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026). |
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| Differences in sex development v4.24 | DMRT1 |
Ida Ertmanska changed review comment from: PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026).; to: PMID: 33057194 Kaplanis et al., 2021 Large exome seq study of Developmental Disorders cohort. 2 patients identified with gonadal dysgenesis and DMRT1 variants: NM_021951.3(DMRT1):c.673C>A (p.Leu225Ile) PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026). |
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| Differences in sex development v4.24 | DMRT1 |
Ida Ertmanska changed review comment from: DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026).; to: PMID: 31745530 Buonocore et al., 2019 Study of a patient cohort with complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25). A patient with CGD and female genital phenotype was heterozygous for variant in DMRT1: c.240G>C, p.Arg80Ser - not reported in gnomAD v4.1.1, inheritance listed as sporadic. Some support for pathogenicity from protein computer modelling. PMID: 27711951 Chauhan et al., 2017 Study of 10 patients with variable DSD. Method: direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes. One patient with complete gonadal dysgenesis was found to be heterozygous for DMRT1: c.416T>A, p.Leu139Gln. PMID: 28295047 Fan et al., 2017 P19 - diagnosed with CGD, 46, XY karyotype with normal SRY; harboured het DMRT1 variant c.251A > G, p.Tyr84Cys - maternally inherited, labelled VUS. As DMRT1 is only expressed in male-specific gonads, authors hypothesise the variant would not be expected to cause a phenotype in the mother. This variant has total of 7 hets reported in gnomAD v4. DMRT1 association with AD "46 XY differences of sex development" has been classified as Definitive in ClinGen (Reproduction and Infertility Expert Panel, 03/18/2026). A separate Definitive association was made between DMRT1 and AD spermatogenic failure. DMRT1 is not yet associated with a disease entity in OMIM (accessed 25th Sept 2026). |
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| Differences in sex development v2.62 | SRY | Eleanor Williams commented on gene: SRY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Differences in sex development v1.32 | SRY | Ivone Leong reviewed gene: SRY: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Differences in sex development | SRY | Ellen McDonagh commented on SRY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Differences in sex development | SRY | Sarah Leigh marked SRY as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Differences in sex development | SRY | Sarah Leigh commented on SRY | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||