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| Structural eye disease v3.57 | GDF3 |
Sarah Leigh changed review comment from: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below. NM_020634.3(GDF3):c.796C>T (p.Arg266Cys) • rs140926412 • https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease • PMID: 19864492; 29260090 NM_020634.3(GDF3):c.584G>A (p.Arg195Gln) • rs146973734 • https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia NM_020634.3(GDF3):c.820C>T (p.Arg274Trp) • rs387906946 • https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia and coloboma NM_020634.3(GDF3):c.914T>C (p.Leu305Pro) • rs387906945 • https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease • PMID: 19864492 three cases: o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance. o 1 patient (2.2) unaffected father of 2.1 o 1 patient with Bilateral iris coloboma NM_020634.3(GDF3):c.974C>T (p.Pro325Leu) • rs566697767 • https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 24281366 o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel o 1 patient unaffected father of the patient above As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro); leading to the assertion that the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers of these variants in the cited publications.; to: A total of five GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below. NM_020634.3(GDF3):c.796C>T (p.Arg266Cys) • rs140926412 • https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease • PMID: 19864492; 29260090 NM_020634.3(GDF3):c.584G>A (p.Arg195Gln) • rs146973734 • https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia NM_020634.3(GDF3):c.820C>T (p.Arg274Trp) • rs387906946 • https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia and coloboma NM_020634.3(GDF3):c.914T>C (p.Leu305Pro) • rs387906945 • https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease • PMID: 19864492 three cases: o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance. o 1 patient (2.2) unaffected father of 2.1 o 1 patient with Bilateral iris coloboma NM_020634.3(GDF3):c.974C>T (p.Pro325Leu) • rs566697767 • https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 24281366 o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel o 1 patient unaffected father of the patient above As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro); leading to the assertion that the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers of these variants in the cited publications. |
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| Structural eye disease v3.57 | GDF3 |
Sarah Leigh changed review comment from: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below. NM_020634.3(GDF3):c.796C>T (p.Arg266Cys) • rs140926412 • https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease • PMID: 19864492; 29260090 NM_020634.3(GDF3):c.584G>A (p.Arg195Gln) • rs146973734 • https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia NM_020634.3(GDF3):c.820C>T (p.Arg274Trp) • rs387906946 • https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia and coloboma NM_020634.3(GDF3):c.914T>C (p.Leu305Pro) • rs387906945 • https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease • PMID: 19864492 three cases: o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance. o 1 patient (2.2) unaffected father of 2.1 o 1 patient with Bilateral iris coloboma NM_020634.3(GDF3):c.974C>T (p.Pro325Leu) • rs566697767 • https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 24281366 o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel o 1 patient unaffected father of the patient above As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro), leading to the assertion the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers in these publications.; to: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below. NM_020634.3(GDF3):c.796C>T (p.Arg266Cys) • rs140926412 • https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease • PMID: 19864492; 29260090 NM_020634.3(GDF3):c.584G>A (p.Arg195Gln) • rs146973734 • https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia NM_020634.3(GDF3):c.820C>T (p.Arg274Trp) • rs387906946 • https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia and coloboma NM_020634.3(GDF3):c.914T>C (p.Leu305Pro) • rs387906945 • https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease • PMID: 19864492 three cases: o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance. o 1 patient (2.2) unaffected father of 2.1 o 1 patient with Bilateral iris coloboma NM_020634.3(GDF3):c.974C>T (p.Pro325Leu) • rs566697767 • https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 24281366 o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel o 1 patient unaffected father of the patient above As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro); leading to the assertion that the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers of these variants in the cited publications. |
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| Structural eye disease v3.57 | GDF3 |
Sarah Leigh edited their review of gene: GDF3: Added comment: A total of GDF3 variants have been reported in PMID: 19864492, 24281366 & 29260090 in patients with ocular phenotypes. It has been noted, that some of the variants have been found in gnomAD v4.0.0 at a high frequency and in unaffected relatives of the patients. A summary of the allele frequencies and other information is presented below. NM_020634.3(GDF3):c.796C>T (p.Arg266Cys) • rs140926412 • https://gnomad.broadinstitute.org/variant/12-7690177-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 4046/1614130 = allele frequency of 0.002507 which could be considered as scoring BS1 depending on the frequency of the disease • PMID: 19864492; 29260090 NM_020634.3(GDF3):c.584G>A (p.Arg195Gln) • rs146973734 • https://gnomad.broadinstitute.org/variant/12-7690389-C-T?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 239/1614062 = allele frequency 0.0001481 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia NM_020634.3(GDF3):c.820C>T (p.Arg274Trp) • rs387906946 • https://gnomad.broadinstitute.org/variant/12-7690153-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 156/1614148 = allele frequency 0.00009665 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 19864492 one patient with Unilateral microphthalmia and coloboma NM_020634.3(GDF3):c.914T>C (p.Leu305Pro) • rs387906945 • https://gnomad.broadinstitute.org/variant/12-7690059-A-G?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 349/1614130 = allele frequency 0.0002162 which could be considered slightly too frequent to score PM2 depending on the frequency of the disease • PMID: 19864492 three cases: o 1 patient (2.1) with Unilateral microphthalmia and incomplete penetrance. o 1 patient (2.2) unaffected father of 2.1 o 1 patient with Bilateral iris coloboma NM_020634.3(GDF3):c.974C>T (p.Pro325Leu) • rs566697767 • https://gnomad.broadinstitute.org/variant/12-7689999-G-A?dataset=gnomad_r4 • gnomAD v4.0.0 exomes & genomes: 77/1613890 = allele frequency 0.00004771 which could be considered as scoring PM2 depending on the frequency of the disease • PMID: 24281366 o 1 patient 11 with microphthalmia and coloboma, also compound heterozygote for two missense mutations in CYP1B1, c.1103G>A, p.(Arg368His), and c.685G>A, p.(Glu229Lys), which is associated with ocular phenotypes (OMIM: 231300 & OMIM: 617315) and is Green on Structural eye disease panel o 1 patient unaffected father of the patient above As a result of this analysis, it seems unlikely that c.796C>T (p.Arg266Cys) is disease causing, due to its high frequency in gnomAD v4.0.0. The contribution of c.974C>T (p.Pro325Leu) to the disease is unknown, as it has only been seen in a patient who was also compound heterozygous for CYP1B1 variants. Plus, c.974C>T (p.Pro325Leu) was also seen in the unaffected father of the patient, as was c.914T>C (p.Leu305Pro), leading to the assertion the effects of GDF3 variants of is subject to reduced penetrance. The variants c.584G>A (p.Arg195Gln) and c.820C>T (p.Arg274Trp) were found at low frequency in gnomAD v4.0.0. and there were no reports of unaffected carriers in these publications.; Changed rating: AMBER |
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| Structural eye disease v0.76 | RS1 | Nicola Ragge reviewed gene: RS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Retinoschisis, 312700; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.48 | RS1 | Ivone Leong edited their review of gene: RS1: Changed phenotypes: Retinoschisis, 312700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.38 | RS1 | Ivone Leong reviewed gene: RS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Oguchi disease-1, Retinitis pigmentosa 47, 258100, 613758; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.15 | RS1 |
Ivone Leong Source NHS GMS was added to RS1. Mode of inheritance for gene RS1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Added phenotypes Retinoschisis, 312700 for gene: RS1 |
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| Structural eye disease v0.2 | RS1 |
Ellen McDonagh gene: RS1 was added gene: RS1 was added to Structural eye disease. Sources: Expert Review Red Mode of inheritance for gene: RS1 was set to Phenotypes for gene: RS1 were set to Eye Disorders |
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