Submissions for variant NM_002693.3(POLG):c.2481-10A>C

dbSNP: rs555280530

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000395822	SCV000394275	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.
GeneDx	RCV000734135	SCV000515716	likely benign	not provided	2018-10-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000468935	SCV000556223	benign	Progressive sclerosing poliodystrophy	2024-11-05	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000734135	SCV000862252	uncertain significance	not provided	2018-07-12	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000468935	SCV000887041	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.2481-10A>C (NP_002684.1:p.=) [GRCH38: NC_000015.10:g.89321863T>G] 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586682	SCV005075851	likely benign	not specified	2024-04-02	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV004586682	SCV005622452	likely benign	not specified	2024-08-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003985773	SCV004761272	likely benign	POLG-related disorder	2019-04-08	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).