Submissions for variant NM_001029883.3(PCARE):c.3044C>A (p.Ser1015Tyr)

gnomAD frequency: 0.00018  dbSNP: rs202196567

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000352886	SCV000429860	uncertain significance	Retinitis pigmentosa	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.
Eurofins Ntd Llc (ga)	RCV000732357	SCV000860307	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000401	SCV001157194	uncertain significance	not specified	2019-05-22	criteria provided, single submitter	clinical testing	The C2orf71 (PCARE) c.3044C>A; p.Ser1015Tyr variant (rs202196567), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 335642). This variant is found in the general population with an overall allele frequency of 0.03% (76/275818 alleles) in the Genome Aggregation Database. The serine at codon 1015 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Ser1015Tyr variant is uncertain at this time.
Invitae	RCV000732357	SCV001213536	uncertain significance	not provided	2023-11-27	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1015 of the PCARE protein (p.Ser1015Tyr). This variant is present in population databases (rs202196567, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with PCARE-related conditions. ClinVar contains an entry for this variant (Variation ID: 335642). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000732357	SCV004700542	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	PCARE: PM2, BP4