ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.3139G>A (p.Val1047Met)

gnomAD frequency: 0.00139  dbSNP: rs35820023
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mayo Clinic Laboratories, Mayo Clinic RCV001527678 SCV007308065 likely benign not provided 2023-11-14 criteria provided, single submitter clinical testing BS1, BP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000321030 SCV006085841 likely benign not specified 2025-05-19 criteria provided, single submitter clinical testing Variant summary: COL1A2 c.3139G>A (p.Val1047Met) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be tolerated. The variant allele was found at a frequency of 0.00037 in 251276 control chromosomes. The observed variant frequency is approximately 13-fold of the estimated maximal expected allele frequency for a pathogenic variant in COL1A2 causing Osteogenesis Imperfecta phenotype (2.8e-05), suggesting the variant may be benign. c.3139G>A has been observed in at least one individual affected with Osteogenesis Imperfecta. However, the variant did not segregate with disease and was found to co-occurr with a COL1A2 exon 11-12 deletion which did segregate with disease within one family (Batkovskyte_2025), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 39513464). ClinVar contains an entry for this variant (Variation ID: 283153). Based on the evidence outlined above, the variant was classified as likely benign.
Ambry Genetics RCV002321951 SCV002607651 likely benign Cardiovascular phenotype 2020-03-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001527678 SCV001157204 likely benign not provided 2024-06-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002229743 SCV001019949 likely benign Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2026-01-26 criteria provided, single submitter clinical testing
GeneDx RCV001527678 SCV000716542 likely benign not provided 2021-05-21 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000321030 SCV000335076 benign not specified 2015-09-25 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003947859 SCV004765623 likely benign COL1A2-related disorder 2021-10-25 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).
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001527678 SCV001970224 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001527678 SCV001808584 likely benign not provided no assertion criteria provided clinical testing

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