Submissions for variant NM_002693.3(POLG):c.2541C>T (p.Ala847=)

gnomAD frequency: 0.00024  dbSNP: rs143810171

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127524	SCV000171101	benign	not specified	2013-10-07	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000470778	SCV000556232	benign	Progressive sclerosing poliodystrophy	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710185	SCV000614715	likely benign	not provided	2017-12-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000710185	SCV000709039	uncertain significance	not provided	2017-06-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316395	SCV000851725	likely benign	Inborn genetic diseases	2017-05-27	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.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000470778	SCV000887047	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.2541C>T (NP_002684.1:p.Ala847=) [GRCH38: NC_000015.10:g.89321793G>A] 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.
Illumina Laboratory Services, Illumina	RCV001117865	SCV001276098	uncertain significance	POLG-Related Spectrum Disorders	2017-04-27	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen	RCV000710185	SCV002545306	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	POLG: BP4, BP7