rs148419444
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004655.4(AXIN2):c.1948C>T(p.Arg650Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,740 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 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. R650H) has been classified as Likely benign.
Frequency
Consequence
NM_004655.4 missense
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.1948C>T | p.Arg650Cys | missense_variant | 8/11 | ENST00000307078.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AXIN2 | ENST00000307078.10 | c.1948C>T | p.Arg650Cys | missense_variant | 8/11 | 1 | NM_004655.4 | P1 | |
AXIN2 | ENST00000375702.5 | c.1753C>T | p.Arg585Cys | missense_variant | 6/9 | 1 | |||
AXIN2 | ENST00000618960.4 | c.1753C>T | p.Arg585Cys | missense_variant | 7/10 | 5 | |||
AXIN2 | ENST00000578251.1 | n.170C>T | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000734 AC: 18AN: 245366Hom.: 1 AF XY: 0.0000601 AC XY: 8AN XY: 133216
GnomAD4 exome AF: 0.0000281 AC: 41AN: 1461492Hom.: 1 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 727024
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74384
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jul 27, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 30, 2023 | The p.R650C variant (also known as c.1948C>T), located in coding exon 7 of the AXIN2 gene, results from a C to T substitution at nucleotide position 1948. The arginine at codon 650 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. 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. - |
Oligodontia-cancer predisposition syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 11, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15735151) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at