ClinVar Miner

Submissions for variant NM_000284.4(PDHA1):c.795A>G (p.Ala265=)

gnomAD frequency: 0.28594  dbSNP: rs1126565
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Total submissions: 10
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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 RCV001271288 SCV001994831 benign Pyruvate dehydrogenase complex deficiency 2021-05-05 reviewed by expert panel curation The allele frequency of the c.795A>G variant in the PDHA1 gene is 13.1% in gnomAD, including more than 9,000 hemizygotes. This allele frequency, and the frequency with which it is seen in hemizygotes in the general population are high enough to be classified as benign based on thresholds defined by the ClinGen PDHA1 Variant Curation Expert Panel (>0.092%; gnomAD- BA1; >16 hemizygotes- BS2). Furthermore, splicing predictors (SPLICE AI) do not predict a deleterious effect (BP7). In summary, this synonymous variant meets criteria to be classified as benign for PDHA1- related pyruvate dehydrogenase deficiency in an X-linked manner. PDHA1-specific ACMG/AMP criteria applied: (BA1, BS2, BP7). This was reviewed with the PDHA1 expert panel on 4/6/2021 and approved on 4/6/2021.
Eurofins Ntd Llc (ga) RCV000078559 SCV000110415 benign not specified 2012-08-09 criteria provided, single submitter clinical testing
GeneDx RCV000078559 SCV000170961 benign not specified 2011-07-06 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.
Ambry Genetics RCV002311553 SCV000846064 benign Inborn genetic diseases 2015-07-12 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
Illumina Laboratory Services, Illumina RCV001166390 SCV001328765 benign Pyruvate dehydrogenase E1-alpha deficiency 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Invitae RCV001166390 SCV001720554 benign Pyruvate dehydrogenase E1-alpha deficiency 2024-02-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000078559 SCV001879404 benign not specified 2021-05-13 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000078559 SCV000152171 likely benign not specified no assertion criteria provided clinical testing Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Mayo Clinic Laboratories, Mayo Clinic RCV000676882 SCV000802696 benign not provided 2016-02-22 no assertion criteria provided clinical testing
Natera, Inc. RCV001271288 SCV001452366 benign Pyruvate dehydrogenase complex deficiency 2020-09-16 no assertion criteria provided clinical testing

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