rs200883019
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004655.4(AXIN2):c.1532C>T(p.Thr511Met) variant causes a missense change. The variant allele was found at a frequency of 0.000569 in 1,613,776 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. T511S) has been classified as Likely benign.
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.1532C>T | p.Thr511Met | missense_variant | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1532C>T | p.Thr511Met | missense_variant | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1532C>T | p.Thr511Met | missense_variant | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1532C>T | p.Thr511Met | missense_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00103 AC: 156AN: 151830Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00124 AC: 312AN: 251244Hom.: 0 AF XY: 0.00128 AC XY: 174AN XY: 135842
GnomAD4 exome AF: 0.000521 AC: 762AN: 1461828Hom.: 1 Cov.: 36 AF XY: 0.000531 AC XY: 386AN XY: 727226
GnomAD4 genome ? AF: 0.00103 AC: 156AN: 151948Hom.: 1 Cov.: 32 AF XY: 0.00143 AC XY: 106AN XY: 74230
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 04, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 11, 2020 | This variant is associated with the following publications: (PMID: 25759019, 23456260) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at