Submissions for variant NM_001384140.1(PCDH15):c.3502-8C>T

gnomAD frequency: 0.00411  dbSNP: rs184144118

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039728	SCV000063417	benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	3502-8C>T in Intron 26 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 0.7% (52/7020) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS).
Eurofins Ntd Llc (ga)	RCV000039728	SCV000228482	benign	not specified	2015-01-02	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000407955	SCV000363159	uncertain significance	Usher syndrome type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000761719	SCV000717935	benign	not provided	2019-02-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000761719	SCV000891904	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	PCDH15: BP4, BS2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039728	SCV000919960	benign	not specified	2018-01-22	criteria provided, single submitter	clinical testing	Variant summary: The PCDH15 c.3502-8C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1152/262912 control chromosomes (6 homozygotes), predominantly observed in the Ashkenazi Jewish subpopulation at a frequency of 0.008337 (83/9956). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic PCDH15 variant (0.0031623), suggesting this is likely a benign polymorphism found primarily in the populations of Ashkenazi Jewish origin. The variant of interest has been reported in a study cohort of UK Usher patients, and was classified by authors as neutral (Le Quesne Stabej_2012). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000761719	SCV001106855	benign	not provided	2025-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000761719	SCV001144872	benign	not provided	2019-02-11	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000039728	SCV001925616	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000761719	SCV001968267	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826581	SCV002094918	benign	Usher syndrome type 1F	2019-10-21	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004534843	SCV004748102	benign	PCDH15-related disorder	2020-04-20	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).