Submissions for variant NM_033056.4(PCDH15):c.5281GCTCCT[1] (p.1761AP[1])

dbSNP: rs397517465

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039752	SCV000063441	likely benign	not specified	2015-04-14	criteria provided, single submitter	clinical testing	p.Ala1763_Pro1764del in exon 33 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 0.8% (18/2306) of East A sian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs397517465). This variant leads to a two codon in-frame delet ion located in the last exon of the gene; however, one study suggests that exon 33 is more tolerant of variation, including truncating variants (Perrault-Micale 2014).
Illumina Laboratory Services, Illumina	RCV004577722	SCV000363120	uncertain significance	Hearing loss, autosomal recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000363120	SCV000363121	uncertain significance	Retinitis pigmentosa-deafness syndrome	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000910500	SCV000604607	likely benign	not provided	2020-07-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000910500	SCV000729390	likely benign	not provided	2021-04-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25307757, 26047050, 33576794, 33111339)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000910500	SCV001055370	likely benign	not provided	2024-01-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001449922	SCV001653321	likely benign	Usher syndrome type 1F	2021-05-18	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001810409	SCV002060006	uncertain significance	Usher syndrome type 1D	2021-10-01	criteria provided, single submitter	clinical testing	NM_033056.3(PCDH15):c.5287_5292del6(A1763_P1764del) is an in-frame deletion classified as a variant of uncertain significance in the context of PCDH15-related disorders. A1763_P1764del has been observed in cases with relevant disease (PMID: 25830873, 27792758). Functional assessments of this variant are not available in the literature. A1763_P1764del has been observed in population frequency databases (gnomAD: EAS 0.57%). In summary, there is insufficient evidence to classify NM_033056.3(PCDH15):c.5287_5292del6(A1763_P1764del) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
CeGaT Center for Human Genetics Tuebingen	RCV000910500	SCV005074119	uncertain significance	not provided	2024-06-01	criteria provided, single submitter	clinical testing	PCDH15: PM4, BS1:Supporting
Natera, Inc.	RCV001449922	SCV002084522	benign	Usher syndrome type 1F	2020-04-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004541130	SCV004796730	likely benign	PCDH15-related disorder	2020-12-30	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).