ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.3405C>T (p.Asp1135=) (rs2307445)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel,ClinGen RCV001526404 SCV001736742 uncertain significance Mitochondrial diseases 2021-05-06 reviewed by expert panel curation The c.3405C>T (p.Asp1135=) variant in POLG is present in population databases at the following frequencies: ESP Allele Frequency: 0.00023 with 0 homozygotes (PM2). This is a silent variant and no change in amino acid (BP7). In summary, there is insufficient evidence to characterize this variant and therefore it remains a variant of uncertain significance for primary mitochondrial disease inherited in an autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: PM2, BP7
GeneDx RCV000431112 SCV000534011 likely benign not specified 2016-11-23 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.
Invitae RCV000633563 SCV000754809 likely benign Progressive sclerosing poliodystrophy 2017-08-24 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000633563 SCV000887279 benign Progressive sclerosing poliodystrophy 2018-10-01 criteria provided, single submitter clinical testing The NM_002693.2:c.3405C>T (NP_002684.1:p.Asp1135=) [GRCH38: NC_000015.10:g.89318618G>A] variant in POLG gene is interpretated to be a 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). BS2:Observation of the variant in controls is inconsistent with penetrance of Mitochondrial DNA depletion syndrome 4A (Alpers type). BP7:The variant is silent with non predicted splice impact. Based on the evidence criteria codes applied, the variant is suggested to be Benign.

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