ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.805G>A (p.Glu269Lys) (rs80109666)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000252636 SCV000302086 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,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 Inc RCV000576391 SCV000677178 benign Alport syndrome 3, autosomal dominant; Alport syndrome, autosomal recessive 2017-06-01 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare 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; 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.
Integrated Genetics/Laboratory Corporation of America 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.

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