Submissions for variant NM_000091.5(COL4A3):c.805G>A (p.Glu269Lys)

gnomAD frequency: 0.02845  dbSNP: rs80109666

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000252636	SCV000302086	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000391399	SCV000428155	benign	Alport syndrome	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics	RCV000252636	SCV000677178	benign	not specified	2022-04-20	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000252636	SCV000711865	benign	not specified	2016-03-21	criteria provided, single submitter	clinical testing	p.Glu269Lys in exon 14 of COL4A3: This variant is not expected to have clinical significance because it has been identified in 15.00% (1291/8608) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs80109666).
GeneDx	RCV000252636	SCV000717136	benign	not specified	2017-10-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000252636	SCV001361060	benign	not specified	2019-09-23	criteria provided, single submitter	clinical testing	Variant summary: COL4A3 c.805G>A (p.Glu269Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.023 in 249418 control chromosomes, predominantly at a frequency of 0.15 within the East Asian subpopulation in the gnomAD database, including 220 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 73-folds over the estimated maximal expected allele frequency for a pathogenic variant in COL4A3 causing Alport Syndrome, autosomal recessive phenotype (0.002), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.805G>A has been reported in the literature in an individual affected with Alport Syndrome, autosomal recessive, however, authors classify the variant as a polymorphism (Zhang_2012). Four ClinVar submissions (evaluation after 2014) cite the variant three times as benign and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001519420	SCV001728287	benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001519420	SCV002506059	benign	not provided	2023-11-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001519420	SCV005243326	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV000391399	SCV001454006	benign	Alport syndrome	2020-09-16	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001519420	SCV001798335	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001519420	SCV001957518	likely benign	not provided		no assertion criteria provided	clinical testing