17-65557888-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004655.4(AXIN2):c.733C>T(p.Pro245Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000522 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. P245A) has been classified as Uncertain significance.
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.733C>T | p.Pro245Ser | missense_variant | 2/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.733C>T | p.Pro245Ser | missense_variant | 2/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.733C>T | p.Pro245Ser | missense_variant | 1/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.733C>T | p.Pro245Ser | missense_variant | 2/10 | 5 | |||
AXIN2 | ENST00000577278.1 | c.733C>T | p.Pro245Ser | missense_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000407 AC: 62AN: 152148Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000632 AC: 159AN: 251446Hom.: 0 AF XY: 0.000618 AC XY: 84AN XY: 135894
GnomAD4 exome AF: 0.000534 AC: 780AN: 1461886Hom.: 0 Cov.: 31 AF XY: 0.000540 AC XY: 393AN XY: 727244
GnomAD4 genome AF: 0.000407 AC: 62AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74450
ClinVar
Submissions by phenotype
not provided Benign:7
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Sep 06, 2022 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | AXIN2: BP4, BS1:Supporting - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function This variant is associated with the following publications: (PMID: 30262796) - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Oligodontia-cancer predisposition syndrome Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 26, 2020 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 17, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 19, 2022 | 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. - |
Ovarian cancer Pathogenic:1
Likely pathogenic, flagged submission | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
AXIN2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 16, 2020 | 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