17-65537324-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_004655.4(AXIN2):c.1712G>A(p.Gly571Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000217 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. G571A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004655.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.1712G>A | p.Gly571Asp | missense_variant, splice_region_variant | 6/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1712G>A | p.Gly571Asp | missense_variant, splice_region_variant | 6/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1712G>A | p.Gly571Asp | missense_variant, splice_region_variant | 5/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1712G>A | p.Gly571Asp | missense_variant, splice_region_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249488Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135020
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461758Hom.: 0 Cov.: 36 AF XY: 0.0000124 AC XY: 9AN XY: 727188
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74328
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 11, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Oligodontia-cancer predisposition syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2023 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at