chr17-65537062-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_004655.4(AXIN2):c.1714G>A(p.Gly572Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000586 in 1,603,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004655.4 missense, splice_region
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.1714G>A | p.Gly572Ser | missense_variant, splice_region_variant | 7/11 | ENST00000307078.10 | NP_004646.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1714G>A | p.Gly572Ser | missense_variant, splice_region_variant | 7/11 | 1 | NM_004655.4 | ENSP00000302625 | P1 | |
AXIN2 | ENST00000375702.5 | c.1712+262G>A | intron_variant | 1 | ENSP00000364854 | |||||
AXIN2 | ENST00000618960.4 | c.1712+262G>A | intron_variant | 5 | ENSP00000478916 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000343 AC: 8AN: 233490Hom.: 0 AF XY: 0.0000470 AC XY: 6AN XY: 127638
GnomAD4 exome AF: 0.0000620 AC: 90AN: 1450838Hom.: 0 Cov.: 34 AF XY: 0.0000665 AC XY: 48AN XY: 721984
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 15, 2023 | 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 15, 2022 | - - |
Oligodontia-cancer predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 02, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 572 of the AXIN2 protein (p.Gly572Ser). This variant is present in population databases (rs753824435, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AXIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 420377). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Colorectal cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 16, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 21, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed in any cases, but was observed in unaffected controls from a melanoma study (Pritchard et al., 2018); This variant is associated with the following publications: (PMID: 26928463, 28108514, 28481359, 29641532) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at