Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000623229 | SCV000742959 | likely pathogenic | Inborn genetic diseases | 2017-09-21 | criteria provided, single submitter | clinical testing | |
| Center for Human Genetics, |
RCV000660306 | SCV000782344 | likely pathogenic | Branchiooculofacial syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV000660306 | SCV005399835 | pathogenic | Branchiooculofacial syndrome | 2024-10-09 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with Branchiooculofacial syndrome. NMD predicted variants are associated with loss of function mechanism, whereas missense mutations within DNA-binding domain are linked to dominant negative mechanism (PMID: 23578821). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 23578821). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD v2 (1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants (DECIPHER; PMID: 23578821, 21204207). (SP) 0702 - Other missense variants comparable to the one identified in this case have strong previous evidence for pathogenicity. p.(Arg248Trp) has been reported in at least three individuals, two of whom were de novo events. In addition, p.(Arg248Gly) has been reported in at least one de novo individual (PMID: 21204207). Both variants have been classified as likely pathogenic/pathogenic by diagnostic laboratories in ClinVar. (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported as de novo events in two affected individuals (DECIPHER) and classified as likely pathogenic by diagnostic laboratories in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |