rs17850455
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_007215.4(POLG2):āc.1247G>Cā(p.Gly416Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0122 in 1,601,138 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. G416G) has been classified as Likely benign.
Frequency
Consequence
NM_007215.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POLG2 | NM_007215.4 | c.1247G>C | p.Gly416Ala | missense_variant | 7/8 | ENST00000539111.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POLG2 | ENST00000539111.7 | c.1247G>C | p.Gly416Ala | missense_variant | 7/8 | 1 | NM_007215.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0100 AC: 1526AN: 152164Hom.: 9 Cov.: 32
GnomAD3 exomes AF: 0.0102 AC: 2567AN: 251182Hom.: 24 AF XY: 0.0100 AC XY: 1358AN XY: 135792
GnomAD4 exome AF: 0.0125 AC: 18053AN: 1448856Hom.: 152 Cov.: 25 AF XY: 0.0122 AC XY: 8770AN XY: 721488
GnomAD4 genome ? AF: 0.0100 AC: 1526AN: 152282Hom.: 9 Cov.: 32 AF XY: 0.00923 AC XY: 687AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 28, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ExAC (NFE): 1087/66520=1.6% - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 08, 2011 | 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. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | POLG2: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 14, 2023 | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 29, 2021 | - - |
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at