ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.2728G>T (p.Ala910Ser)

gnomAD frequency: 0.00026  dbSNP: rs139175351
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Total submissions: 7
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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 RCV000825424 SCV000966722 uncertain significance not specified 2018-12-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala910Ser var iant in PCDH15 has been reported in three individuals from Saudi Arabia with hea ring loss (Dallol 2016), and it has also been reported in ClinVar (Variation ID: 550483). This variant has also been identified in 0.12% (29/24020) African chro mosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction t ools and conservation analysis do not provide strong support for or against an i mpact to the protein. In summary, while the clinical significance of the p.Ala91 0Ser variant is uncertain, its frequency suggests that it is more likely to be b enign. ACMG/AMP Criteria applied: BS1_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001071361 SCV001236659 likely benign not provided 2024-11-18 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001810467 SCV002060314 uncertain significance Usher syndrome type 1D 2021-11-08 criteria provided, single submitter clinical testing NM_033056.3(PCDH15):c.2728G>T(A910S) is a missense variant classified as a variant of uncertain significance in the context of PCDH15-related disorders. A910S has been observed in cases with relevant disease (PMID: 27766948). Functional assessments of this variant are not available in the literature. A910S has been observed in population frequency databases (gnomAD: AFR 0.11%). In summary, there is insufficient evidence to classify NM_033056.3(PCDH15):c.2728G>T(A910S) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Center for Human Genetics Tuebingen RCV001071361 SCV005051299 likely benign not provided 2024-05-01 criteria provided, single submitter clinical testing PCDH15: BS1:Supporting
Natera, Inc. RCV000665239 SCV001459221 uncertain significance Usher syndrome type 1F 2020-09-16 no assertion criteria provided clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004817867 SCV005069487 uncertain significance Optic atrophy 2023-01-01 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004735733 SCV005353173 uncertain significance PCDH15-related disorder 2024-07-26 no assertion criteria provided clinical testing The PCDH15 c.2728G>T variant is predicted to result in the amino acid substitution p.Ala910Ser. This variant has been reported in three unrelated patients with hearing loss, although conclusive evidence of pathogenicity was not presented (described as p.Ala915Ser, Dallol et al. 2016. PubMed ID: 27766948). This variant is reported in 0.12% of alleles in individuals of African descent in gnomAD, which may be too common to be a primary cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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