rs786201772
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001048174.2(MUTYH):c.730C>T(p.Pro244Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P244A) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.814C>T | p.Pro272Ser | missense_variant | 10/16 | ENST00000710952.2 | |
MUTYH | NM_001048174.2 | c.730C>T | p.Pro244Ser | missense_variant | 10/16 | ENST00000456914.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.814C>T | p.Pro272Ser | missense_variant | 10/16 | NM_001128425.2 | |||
MUTYH | ENST00000456914.7 | c.730C>T | p.Pro244Ser | missense_variant | 10/16 | 1 | NM_001048174.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250128Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135470
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461808Hom.: 0 Cov.: 36 AF XY: 0.00000825 AC XY: 6AN XY: 727198
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 2 Uncertain:5
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 272 of the MUTYH protein (p.Pro272Ser). This variant is present in population databases (rs786201772, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 184896). 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. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Human Genetics Bochum, Ruhr University Bochum | Oct 21, 2022 | ACMG criteria used to clasify this variant: PM2_SUP_MOD, PP3 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 26, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 23, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jun 28, 2023 | This missense variant replaces proline with serine at codon 272 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250128 chromosomes 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. - |
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 20, 2022 | The p.P272S variant (also known as c.814C>T), located in coding exon 10 of the MUTYH gene, results from a C to T substitution at nucleotide position 814. The proline at codon 272 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 01, 2022 | This missense variant replaces proline with serine at codon 272 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250128 chromosomes 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. - |
Lynch syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Human Genetics Bochum, Ruhr University Bochum | Oct 24, 2022 | ACMG criteria used to clasify this variant: PM2, PP3 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at