17-65537593-G-A
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_004655.4(AXIN2):c.1443C>T(p.Leu481Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,605,590 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. L481L) has been classified as Benign.
Frequency
Consequence
NM_004655.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- oligodontia-cancer predisposition syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
- tooth agenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- craniosynostosisInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1443C>T | p.Leu481Leu | synonymous_variant | Exon 6 of 11 | 1 | NM_004655.4 | ENSP00000302625.5 | ||
AXIN2 | ENST00000375702.5 | c.1443C>T | p.Leu481Leu | synonymous_variant | Exon 5 of 9 | 1 | ENSP00000364854.5 | |||
AXIN2 | ENST00000618960.4 | c.1443C>T | p.Leu481Leu | synonymous_variant | Exon 6 of 10 | 5 | ENSP00000478916.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00 AC: 0AN: 233798 AF XY: 0.00
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453580Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 722598 show subpopulations
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74216 show subpopulations
ClinVar
Submissions by phenotype
Oligodontia-cancer predisposition syndrome Uncertain:1Benign:2
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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
- -
Hereditary cancer-predisposing syndrome Benign:2
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. -
PM2+BP4+BP6+BP7 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at