Submissions for variant NM_002693.3(POLG):c.*49G>A

dbSNP: rs758880377

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000361772	SCV000394240	uncertain significance	Fanconi anemia complementation group I	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.
Illumina Laboratory Services, Illumina	RCV000267134	SCV000394241	uncertain significance	POLG-Related Spectrum Disorders	2016-06-14	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000758389	SCV000887066	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.*49G>A (NP_002684.1:p.=) [GRCH38: NC_000015.10:g.89316702C>T] variant in FANCI 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 FANCI 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.
PreventionGenetics, part of Exact Sciences	RCV003985770	SCV004781194	likely benign	POLG-related disorder	2021-03-19	criteria provided, single submitter	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).