Submissions for variant NM_002693.3(POLG):c.2853C>T (p.Tyr951=)

gnomAD frequency: 0.00078  dbSNP: rs41546712

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000186650	SCV000171106	benign	not specified	2014-01-24	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.
Eurofins Ntd Llc (ga)	RCV000186650	SCV000203327	likely benign	not specified	2017-06-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000471041	SCV000556229	likely benign	Progressive sclerosing poliodystrophy	2024-01-29	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000712796	SCV000843327	likely benign	not provided	2018-05-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316396	SCV000851230	likely benign	Inborn genetic diseases	2016-09-16	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	RCV000471041	SCV000887082	benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.2853C>T (NP_002684.1:p.Tyr951=) [GRCH38: NC_000015.10:g.89320894G>A] variant in POLG gene is interpretated to be a 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). BS2:Observation of the variant in controls is inconsistent with penetrance of Mitochondrial DNA depletion syndrome 4A (Alpers type). BP4:Computational evidence/predictors indicate no impact on the POLG structure, function, or protein-protein interaction. Based on the evidence criteria codes applied, the variant is suggested to be Benign.
Illumina Laboratory Services, Illumina	RCV001116417	SCV001274490	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	RCV000712796	SCV001334802	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	POLG: BP4, BP7
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847751	SCV002105574	likely benign	Hereditary spastic paraplegia	2021-03-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000712796	SCV001741885	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000712796	SCV001928679	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000712796	SCV001975694	likely benign	not provided		no assertion criteria provided	clinical testing