17-65558398-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004655.4(AXIN2):c.223C>G(p.Leu75Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,264 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 Uncertain significance (★).
Frequency
Consequence
NM_004655.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.223C>G | p.Leu75Val | missense_variant | Exon 2 of 11 | 1 | NM_004655.4 | ENSP00000302625.5 | ||
ENSG00000266076 | ENST00000577662.1 | n.*399C>G | non_coding_transcript_exon_variant | Exon 4 of 7 | 2 | ENSP00000462418.1 | ||||
ENSG00000266076 | ENST00000577662.1 | n.*399C>G | 3_prime_UTR_variant | Exon 4 of 7 | 2 | ENSP00000462418.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248222Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134016
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1454264Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 722176
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.L75V variant (also known as c.223C>G), located in coding exon 1 of the AXIN2 gene, results from a C to G substitution at nucleotide position 223. The leucine at codon 75 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at