Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
INGEBI, |
RCV001251624 | SCV001427358 | likely pathogenic | Nonsyndromic genetic hearing loss | 2020-08-04 | criteria provided, single submitter | clinical testing | Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: The c.632G>A, p.(Cys211Tyr) variant is absent from population databases (gnomAD, GO-ESP, 1000 genomes) meeting PM2 criteria. It has been identified in trans with del(GJB6-D13S1830) variant in two siblings with moderate postlingual hearing loss. There was an unaffected brother who only carried the p.(Cys211Tyr) variant (PMID: 24158611; PM3, PP1_Supporting). Finally, computational evidence predicted a pathogenic effect of the mutation to the protein (REVEL: 0.970) applying to PP3. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive non-syndromic hearing loss (PM2, PM3, PP1_Supporting and PP3). |