chr17-65536450-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004655.4(AXIN2):c.2011C>T(p.Arg671Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,746 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R671P) has been classified as Likely benign.
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.2011C>T | p.Arg671Cys | missense_variant | 8/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.2011C>T | p.Arg671Cys | missense_variant | 8/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1816C>T | p.Arg606Cys | missense_variant | 6/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1816C>T | p.Arg606Cys | missense_variant | 7/10 | 5 | |||
AXIN2 | ENST00000578251.1 | n.233C>T | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000264 AC: 4AN: 151632Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000328 AC: 8AN: 244106Hom.: 0 AF XY: 0.0000377 AC XY: 5AN XY: 132756
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460998Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 726830
GnomAD4 genome AF: 0.0000264 AC: 4AN: 151748Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74216
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 04, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Dec 12, 2021 | - - |
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 671 of the AXIN2 protein (p.Arg671Cys). This variant is present in population databases (rs754506970, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 408768). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Colorectal cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 30, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 08, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with history of sarcoma, as well as in both cases and control groups from breast cancer and melanoma case-control studies (Ballinger et al., 2016; Melloni et al. 2017; Pritchard et al., 2018); This variant is associated with the following publications: (PMID: 24145436, 23525077, 27498913, 24362935, 15735151, 28569218, 29641532) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at