ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.4925G>A (p.Gly1642Asp)

gnomAD frequency: 0.00005  dbSNP: rs745335831
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000608419 SCV000712452 uncertain significance not specified 2016-09-22 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Gly1642Asp va riant in PCDH15 has not been previously reported in individuals with hearing los s or Usher syndrome. This variant has been identified in 1/10406 African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs745335831); however, this frequency is not high enough to rule out a pat hogenic role. The glycine (Gly) at position 1642 is not conserved in mammals or evolutionarily distant species, supporting that a change at this position may be tolerated. Additional computational prediction tools suggest that the p.Gly1642 Asp variant may not impact the protein, though this information is not predictiv e enough to rule out pathogenicity. In summary, while the clinical significance of the p.Gly1642Asp variant is uncertain, these data suggest that it is more lik ely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV001868023 SCV002294155 uncertain significance not provided 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 1642 of the PCDH15 protein (p.Gly1642Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs745335831, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with PCDH15-related conditions. ClinVar contains an entry for this variant (Variation ID: 505300). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002483677 SCV002793256 uncertain significance Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2021-11-10 criteria provided, single submitter clinical testing
Natera, Inc. RCV001829707 SCV002087284 uncertain significance Usher syndrome type 1F 2020-03-27 no assertion criteria provided clinical testing

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