rs1057517460
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001048174.2(MUTYH):c.20C>T(p.Ala7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001048174.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.62C>T | p.Ala21Val | missense_variant | 2/16 | ENST00000710952.2 | |
MUTYH | NM_001048174.2 | c.20C>T | p.Ala7Val | missense_variant | 2/16 | ENST00000456914.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.62C>T | p.Ala21Val | missense_variant | 2/16 | NM_001128425.2 | |||
MUTYH | ENST00000456914.7 | c.20C>T | p.Ala7Val | missense_variant | 2/16 | 1 | NM_001048174.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461818Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727218
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Sep 08, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 05, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 371682). This missense change has been observed in individual(s) with adenomatous polyposis and/or colorectal cancer (PMID: 17949294, 31780696). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 21 of the MUTYH protein (p.Ala21Val). - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Aug 30, 2022 | This missense variant replaces alanine with valine at codon 21 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with multiple colorectal adenomas (PMID: 17949294). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The p.A21V variant (also known as c.62C>T), located in coding exon 2 of the MUTYH gene, results from a C to T substitution at nucleotide position 62. The alanine at codon 21 is replaced by valine, an amino acid with similar properties. This alteration was reported (referred to as c.61C>T) in an individual from a cohort of APC negative individuals with more than 5 colorectal adenomas (Olschwang S et al. Genet. Test., 2007;11:315-20). This amino acid position is not 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. - |
Gastric cancer;C3272841:Familial adenomatous polyposis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at