Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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 |
RCV000078559 | SCV000110415 | benign | not specified | 2012-08-09 | criteria provided, single submitter | clinical testing | |
Gene |
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, |
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, |
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, |
RCV000676882 | SCV000802696 | benign | not provided | 2016-02-22 | no assertion criteria provided | clinical testing | |
Natera, |
RCV001271288 | SCV001452366 | benign | Pyruvate dehydrogenase complex deficiency | 2020-09-16 | no assertion criteria provided | clinical testing |