17-65530080-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004655.4(AXIN2):c.2428G>A(p.Asp810Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000255 in 1,614,174 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.2428G>A | p.Asp810Asn | missense_variant | Exon 11 of 11 | 1 | NM_004655.4 | ENSP00000302625.5 | ||
AXIN2 | ENST00000375702.5 | c.2233G>A | p.Asp745Asn | missense_variant | Exon 9 of 9 | 1 | ENSP00000364854.5 | |||
AXIN2 | ENST00000618960.4 | c.2233G>A | p.Asp745Asn | missense_variant | Exon 10 of 10 | 5 | ENSP00000478916.1 |
Frequencies
GnomAD3 genomes AF: 0.00115 AC: 175AN: 152188Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000263 AC: 66AN: 251282Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135850
GnomAD4 exome AF: 0.000161 AC: 236AN: 1461868Hom.: 2 Cov.: 31 AF XY: 0.000125 AC XY: 91AN XY: 727240
GnomAD4 genome AF: 0.00115 AC: 175AN: 152306Hom.: 1 Cov.: 33 AF XY: 0.000994 AC XY: 74AN XY: 74466
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:2
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Hereditary cancer-predisposing syndrome Benign:2
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. -
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not provided Uncertain:1
This variant is denoted AXIN2 c.2428G>A at the cDNA level, p.Asp810Asn (D810N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). This variant was observed in at least one individual with breast or gynecological cancer, as well as individuals with colon cancer (DeRycke 2017, Dominguez-Valentin 2018). AXIN2 Asp810Asn was observed at an allele frequency of 0.35% (83/24,028) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is located in the DIX domain (Salahshor 2005). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether AXIN2 Asp810Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. -
Oligodontia-cancer predisposition syndrome Benign:1
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AXIN2-related disorder Benign:1
This variant is classified as likely 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