rs748632114
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_004655.4(AXIN2):c.2034G>T(p.Leu678=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L678L) has been classified as Likely benign.
Frequency
Consequence
NM_004655.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AXIN2 | NM_004655.4 | c.2034G>T | p.Leu678= | synonymous_variant | 8/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.2034G>T | p.Leu678= | synonymous_variant | 8/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1839G>T | p.Leu613= | synonymous_variant | 6/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1839G>T | p.Leu613= | synonymous_variant | 7/10 | 5 | |||
AXIN2 | ENST00000578251.1 | n.256G>T | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461416Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727028
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2019 | 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 | Jan 02, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 24, 2014 | This variant is denoted AXIN2 c.2034G>T at the DNA level. Although the variant is silent at the coding level, preserving a Leucine at codon 678, it is predicted to activate a cryptic splice acceptor site possibly leading to abnormal splicing. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. AXIN2 2034G>T was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The nucleotide which is altered, a guanine (G) at base 2034, is highly variable across species. Based on the currently available information, it is unclear whether AXIN2 2034G>T is pathogenic or benign. We consider it to be a variant of uncertain significance. - |
Oligodontia-cancer predisposition syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at