Submissions for variant NM_033056.4(PCDH15):c.5557A>C (p.Met1853Leu)

gnomAD frequency: 0.00020  dbSNP: rs145903555

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154360	SCV000204023	likely benign	not specified	2016-02-25	criteria provided, single submitter	clinical testing	p.Met1853Leu in exon 33 of PCDH15: This variant is not expected to have clinica l significance because it has been identified in 0.4% (61/16510) of South Asian chromosomes, including 1 homozygote, by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs145903555). Although this variant has been previously reported in compound heterozygosity with a pathogenic variant i n one Ashkenazi Jewish individual with Usher syndrome, it was also detected in 0 .32% (9/2836) of control chromosomes from various Ashkenazi and non-Ashkenazi Je wish populations. In addition, computational prediction tools and conservation a nalyses suggest that this variant may not impact the protein. In summary, due t o the frequency of this variant in the general population, it is likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000879612	SCV001022656	benign	not provided	2024-11-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001104785	SCV001261672	likely benign	Usher syndrome type 1	2017-06-24	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000879612	SCV001778452	likely benign	not provided	2021-03-30	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30245029, 21569298, 18727382, 15028842, 12711741, 25262649, 20672374)
CeGaT Center for Human Genetics Tuebingen	RCV000879612	SCV004701348	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	PCDH15: BP4
Clinical Genetics, Academic Medical Center	RCV000154360	SCV001921743	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000879612	SCV001969236	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826830	SCV002080805	likely benign	Usher syndrome type 1F	2020-01-27	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544404	SCV004774383	likely benign	PCDH15-related disorder	2022-03-10	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).