Submissions for variant NM_002693.3(POLG):c.2735-7C>G

gnomAD frequency: 0.00128  dbSNP: rs200372494

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127528	SCV000171105	benign	not specified	2013-06-27	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	RCV000463735	SCV000556225	benign	Progressive sclerosing poliodystrophy	2024-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000127528	SCV000705169	likely benign	not specified	2016-12-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000658724	SCV000780511	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	POLG: BP4, BS2
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000463735	SCV000887297	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.2735-7C>G (NP_002684.1:p.=) [GRCH38: NC_000015.10:g.89321019G>C] 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. BP6:Reputable source(s) without shared data suggest the variant is benign. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign.
Illumina Laboratory Services, Illumina	RCV001116419	SCV001274492	uncertain significance	POLG-Related Spectrum Disorders	2018-01-12	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.