ClinVar Miner

Submissions for variant NM_001005361.3(DNM2):c.1384A>G (p.Thr462Ala)

gnomAD frequency: 0.00011  dbSNP: rs201575500
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000459689 SCV000410365 benign Charcot-Marie-Tooth disease dominant intermediate B 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.
Illumina Laboratory Services, Illumina RCV000331170 SCV000410366 likely benign Autosomal dominant centronuclear myopathy 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV000459689 SCV000553368 likely benign Charcot-Marie-Tooth disease dominant intermediate B 2024-01-11 criteria provided, single submitter clinical testing
GeneDx RCV000766564 SCV000577324 uncertain significance not provided 2017-04-04 criteria provided, single submitter clinical testing The T462A variant has been previously reported as a variant of unknown significance in an individual with congenital myopathy who harbored additional variants in other neuromuscular-related genes (Savarese et al., 2014). The T462A variant is observed in 19/66618 (0.03%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and missense variant in a nearby residue (R465W) has been reported in the Human Gene Mutation Database in association with centronuclear myopathy (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function.
Athena Diagnostics RCV000489408 SCV000613148 benign not specified 2020-03-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002379210 SCV002699014 likely benign Inborn genetic diseases 2020-02-20 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.
Revvity Omics, Revvity RCV000766564 SCV003830497 uncertain significance not provided 2023-09-06 criteria provided, single submitter clinical testing

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