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]

Link to SEPIO compliant JSON-LD document

Variant: NM_002693.2(POLG):c.3239G>C (p.Ser1080Thr)

CA316750

206553 (ClinVar)

Gene: POLG

Condition: mitochondrial disease

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e7760185-21c1-40f7-bd28-047f6a75ea1c

HGVS expressions

NM_002693.2:c.3239G>C

NM_002693.2(POLG):c.3239G>C (p.Ser1080Thr)

ENST00000268124.11:c.3239G>C

ENST00000530292.3:n.2840G>C

ENST00000635986.2:c.*309G>C

ENST00000636774.1:c.*1806G>C

ENST00000637238.1:n.2048G>C

ENST00000637264.1:n.2311G>C

ENST00000666746.1:n.2816G>C

ENST00000672071.1:n.3437G>C

ENST00000672695.1:n.416G>C

ENST00000672923.2:n.3239G>C

ENST00000268124.9:c.3239G>C

ENST00000442287.6:c.3239G>C

ENST00000530292.2:n.323G>C

ENST00000631044.2:c.*2663G>C

NM_001126131.1:c.3239G>C

NM_001126131.2:c.3239G>C

NM_002693.3:c.3239G>C

NC_000015.10:g.89318965C>G

CM000677.2:g.89318965C>G

NC_000015.9:g.89862196C>G

CM000677.1:g.89862196C>G

NC_000015.8:g.87663200C>G

NG_008218.1:g.20831G>C

NG_011736.1:g.80003C>G

NG_008218.2:g.20831G>C

Uncertain Significance

PM2 BP5

BP4

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.3293 G>C (p.Ser1098Thr) variant in POLG is observed at an allele frequency of 0.003% in gnomAD (PM2). There is no prediction tool evidence available. This variant was found in a proband of Chinese ancestry with congenital cataracts who harbored a pathogenic variant in the PITX3 gene (BP5; PMID 30894134). 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: PM2, BP5.

PM2

0.00003

BP5

see supplemental data for POLG variant found in this case of congenital cataracts

BP4

conflicting data

Approved on: 2021-05-07

Published on: 2021-05-07

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