ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1386G>A (p.Ser462=)

gnomAD frequency: 0.00061  dbSNP: rs62640034
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000127560 SCV000171137 benign not specified 2014-04-17 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.
Eurofins Ntd Llc (ga) RCV000725999 SCV000341136 uncertain significance not provided 2016-11-15 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000402563 SCV000394292 uncertain significance POLG-Related Spectrum Disorders 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.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000758496 SCV000887213 likely benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.1386G>A (NP_002684.1:p.Ser462=) [GRCH38: NC_000015.10:g.89327214C>T] variant in POLG gene is interpretated to be a Likely Benign based on ACMG guidelines (PMID: 25741868). This variant meets the following evidence codes reported in the ACMG-guideline. BS1:The minor allele frequency of this allele is high for Mitochondrial DNA depletion syndrome 4A (Alpers type). BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. BP7:The variant is silent with non predicted splice impact. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV000758496 SCV001005860 likely benign Progressive sclerosing poliodystrophy 2024-01-19 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001847758 SCV002105548 likely benign Hereditary spastic paraplegia 2021-06-16 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003985733 SCV004775161 likely benign POLG-related disorder 2020-04-20 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).

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