Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_002693.2(POLG):c.3561G>C (p.Arg1187=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA288989

129997 (ClinVar)

Gene: POLG

Condition: mitochondrial disease

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e7f0e10c-d8ab-4428-8d1f-4e0c7f8e7521

Approved on: 2021-05-06

Published on: 2021-05-06

HGVS expressions

NM_002693.2:c.3561G>C

NM_002693.2(POLG):c.3561G>C (p.Arg1187=)

ENST00000268124.11:c.3561G>C

ENST00000530292.3:n.3261G>C

ENST00000635986.2:c.*631G>C

ENST00000636774.1:c.*2165G>C

ENST00000637042.1:n.85G>C

ENST00000637238.1:n.2469G>C

ENST00000637264.1:n.2573G>C

ENST00000666746.1:n.3138G>C

ENST00000672071.1:n.4763G>C

ENST00000672695.1:n.1340G>C

ENST00000672923.2:n.3561G>C

ENST00000268124.9:c.3561G>C

ENST00000442287.6:c.3561G>C

ENST00000526671.1:n.371G>C

ENST00000530292.2:n.744G>C

ENST00000631044.2:c.*2985G>C

NM_001126131.1:c.3561G>C

NM_001126131.2:c.3561G>C

NM_002693.3:c.3561G>C

NC_000015.10:g.89317458C>G

CM000677.2:g.89317458C>G

NC_000015.9:g.89860689C>G

CM000677.1:g.89860689C>G

NC_000015.8:g.87661693C>G

NG_008218.1:g.22338G>C

NG_011736.1:g.78496C>G

NG_008218.2:g.22338G>C

Uncertain Significance

PM2 BS2 BP7

Evidence Links 0

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The c.3561 G>C (p.Arg1187=) variant in POLG is present in population databases 1000 genome 0.03%, ExAC at 0.002%, and gnomAD at 0.002% (PM2; observed < 0.05% frequency). Computational prediction tool Revel unavailable given limited data. This variant was observed in homozygotes in 13 cases in gnomAD and 1 case in ExAC (BS2). This variant is a coding synonymous change (BP7). In summary, there is not sufficient evidence to characterize this variant as pathogenic or benign, therefore it is characterized as a variant of uncertain significance for primary mitochondrial disease inherited in a autosomal recessive manner. ntDNA Mitochondrial ACMG-AMP Criteria for POLG applied: BS2, PM2, BP7.

PM2

Rule < 0.05% 1000Genome minor allele 0.02723 gnomAD 0.00239 ExAC 0.00203

BS2

Observed in homozygotes 13 in gnomAD and 1 in ExAC

BP7

Synonymous change

Curation History

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