Submissions for variant NM_033056.4(PCDH15):c.5296_5304dup (p.Ala1766_Pro1768dup)

dbSNP: rs397517466

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039753	SCV000063442	likely benign	not specified	2017-03-29	criteria provided, single submitter	clinical testing	c.5296_5304dupGCTCCTCCT (p.Ala1766_Pro1768dup) in exon 33 of PCDH15: This varian t is a duplication of 9 bases at position c.5296 in the last exon of gene (exon 33) and is not predicted to alter the protein reading-frame. Although the possib le impact of this on protein function is unknown; several nearby inframe deleti ons and duplications have been identified in large population databases, and thi s exon 33 has been reported to be tolerant to variation, including loss of funct ion variants (Perreault-Micale 2014). The variant has also been identified in 13 /28846 of Latino chromosomes by the Genome Aggregation Database (gnomAD, http:// gnomad.broadinstitute.org; dbSNP rs397517466). In summary, these data suggest th at the variant is likely benign.
Eurofins Ntd Llc (ga)	RCV000734418	SCV000862559	uncertain significance	not provided	2018-07-18	criteria provided, single submitter	clinical testing
Invitae	RCV000734418	SCV001414582	uncertain significance	not provided	2022-10-28	criteria provided, single submitter	clinical testing	This variant, c.5296_5304dup, results in the insertion of 3 amino acid(s) of the PCDH15 protein (p.Ala1766_Pro1768dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 46494). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
GeneDx	RCV000734418	SCV002756998	uncertain significance	not provided	2022-07-05	criteria provided, single submitter	clinical testing	In-frame duplication of 3 amino acids in a non-repeat region; Has not been previously published as pathogenic or benign in association with a PCDH15-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 28157192)
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000734418	SCV001797886	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000734418	SCV001965372	uncertain significance	not provided		no assertion criteria provided	clinical testing