Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000670158 | SCV000794982 | uncertain significance | Usher syndrome type 1F | 2017-10-24 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002499169 | SCV002813410 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F | 2021-10-20 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV000670158 | SCV003761040 | uncertain significance | Usher syndrome type 1F | 2023-01-24 | criteria provided, single submitter | curation | The p.Ala1376Asp variant in PCDH15 has been reported in 1 individual, in the compound heterozygous state, with Usher syndrome type 1F (PMID: 28000701) and has been identified in 0.005% (1/18394) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs752371584). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 554510) and has been interpreted as a variant of uncertain significance by Counsyl. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ala1376Asp variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting, PM3 (Richards 2015). |