17-65537463-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004655.4(AXIN2):āc.1573C>Gā(p.Pro525Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00154 in 1,613,936 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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AXIN2 | ENST00000307078.10 | c.1573C>G | p.Pro525Ala | missense_variant | Exon 6 of 11 | 1 | NM_004655.4 | ENSP00000302625.5 | ||
AXIN2 | ENST00000375702.5 | c.1573C>G | p.Pro525Ala | missense_variant | Exon 5 of 9 | 1 | ENSP00000364854.5 | |||
AXIN2 | ENST00000618960.4 | c.1573C>G | p.Pro525Ala | missense_variant | Exon 6 of 10 | 5 | ENSP00000478916.1 |
Frequencies
GnomAD3 genomes AF: 0.00858 AC: 1303AN: 151946Hom.: 18 Cov.: 32
GnomAD3 exomes AF: 0.00201 AC: 505AN: 251430Hom.: 15 AF XY: 0.00148 AC XY: 201AN XY: 135906
GnomAD4 exome AF: 0.000800 AC: 1170AN: 1461872Hom.: 22 Cov.: 35 AF XY: 0.000688 AC XY: 500AN XY: 727244
GnomAD4 genome AF: 0.00861 AC: 1309AN: 152064Hom.: 19 Cov.: 32 AF XY: 0.00810 AC XY: 602AN XY: 74298
ClinVar
Submissions by phenotype
not specified Benign:6
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. -
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Variant summary: AXIN2 c.1573C>G (p.Pro525Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0026 in 277090 control chromosomes in the gnomAD database, including 14 homozygotes. The observed variant frequency is approximately 19-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in AXIN2 causing Colorectal Cancer phenotype (0.00014), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1573C>G in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
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Oligodontia-cancer predisposition syndrome Benign:2
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not provided Benign:2
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Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as 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. -
AXIN2-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at