Submissions for variant NM_002693.3(POLG):c.3482+6C>T

dbSNP: rs55779802

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127539	SCV000171116	benign	not specified	2013-10-03	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)	RCV000726414	SCV000344482	uncertain significance	not provided	2017-08-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000316461	SCV000394265	uncertain significance	POLG-Related Spectrum Disorders	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000559092	SCV000630152	likely benign	Progressive sclerosing poliodystrophy	2024-01-29	criteria provided, single submitter	clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000559092	SCV000887301	likely benign	Progressive sclerosing poliodystrophy	2018-10-01	criteria provided, single submitter	clinical testing	The NM_002693.2:c.3482+6C>T (NP_002684.1:p.=) [GRCH38: NC_000015.10:g.89318535G>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. Based on the evidence criteria codes applied, the variant is suggested to be Likely Benign.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768049	SCV000898894	uncertain significance	Progressive sclerosing poliodystrophy; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1; Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis; Mitochondrial DNA depletion syndrome 4b	2021-03-30	criteria provided, single submitter	clinical testing	POLG NM_002693 exon 21 c.3482+6C>T: This variant has not been reported in the literature but is present in 0.1% (35/23996) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs55779802). This variant is present in ClinVar (Variation ID:138760). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences	RCV000559092	SCV001244667	uncertain significance	Progressive sclerosing poliodystrophy	2019-07-05	criteria provided, single submitter	research
Athena Diagnostics	RCV000127539	SCV001879841	likely benign	not specified	2021-06-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847754	SCV002105586	uncertain significance	Hereditary spastic paraplegia	2018-10-01	criteria provided, single submitter	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV003441747	SCV003926469	likely benign	Mitochondrial DNA depletion syndrome 4b		no assertion criteria provided	clinical testing