NM_002693.3(POLG):c.3483-14T>C AND not specified

Germline classification:: Benign/Likely benign (2 submissions)
Last evaluated:: Sep 18, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000127544.3

Allele description [Variation Report for NM_002693.3(POLG):c.3483-14T>C]

NM_002693.3(POLG):c.3483-14T>C

Gene:

POLG:DNA polymerase gamma, catalytic subunit [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_002693.3(POLG):c.3483-14T>C

Other names:

NM_002693.2(POLG):c.3483-14T>C

HGVS:

NC_000015.10:g.89317550A>G
NG_008218.2:g.22246T>C
NG_011736.1:g.78588A>G
NM_001126131.2:c.3483-14T>C
NM_002693.3:c.3483-14T>CMANE SELECT
LRG_765t1:c.3483-14T>C
LRG_500:g.78588A>G
LRG_765:g.22246T>C
NC_000015.9:g.89860781A>G
NC_000015.9:g.89860781A>G
NM_002693.2:c.3483-14T>C

Links:

dbSNP: rs587781119

NCBI 1000 Genomes Browser:

rs587781119

Molecular consequence:

NM_001126131.2:c.3483-14T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_002693.3:c.3483-14T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000171121	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Mar 28, 2014)	germline	clinical testing	Citation Link,
SCV004099949	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Sep 18, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000171121

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Mar 28, 2014)

germline

clinical testing

Citation Link,

SCV004099949

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Sep 18, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000171121.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004099949.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: POLG c.3483-14T>C alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.8e-05 in 251070 control chromosomes (gnomAD). To our knowledge, no occurrence of c.3483-14T>C in individuals affected with POLG-Related Spectrum Disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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