rs202240122
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The ENST00000372098.7(MUTYH):c.42C>T(p.Ile14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,613,946 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).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
MUTYH
ENST00000372098.7 synonymous
ENST00000372098.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.50
Genes affected
MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 1-45334506-G-A is Benign according to our data. Variant chr1-45334506-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 138307.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=8, Benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=1.5 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.42C>T | p.Ile14= | synonymous_variant | 2/16 | ENST00000710952.2 | |
MUTYH | NM_001048174.2 | c.-1C>T | 5_prime_UTR_variant | 2/16 | ENST00000456914.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.42C>T | p.Ile14= | synonymous_variant | 2/16 | NM_001128425.2 | |||
MUTYH | ENST00000456914.7 | c.-1C>T | 5_prime_UTR_variant | 2/16 | 1 | NM_001048174.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000954 AC: 24AN: 251476Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135912
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GnomAD4 exome AF: 0.000173 AC: 253AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.000179 AC XY: 130AN XY: 727214
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:9
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Familial adenomatous polyposis 2 Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Jul 14, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 10, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 09, 2014 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 29, 2016 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 22, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 29, 2019 | - - |
Carcinoma of colon Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The MUTYH p.Ile14= variant was identified in 1 of 658 proband chromosomes (frequency: 0.0015) from individuals or families with FAP (Aretz_2006). The variant was also identified in dbSNP (ID: rs202240122) as With Likely benign, Uncertain significance allele, and in ClinVar (classified as benign by GeneDx; as likely benign by Ambry Genetics, Invitae, Color Genomics). The variant was not identified in COGR or UMD-LSDB databases. The variant was identified in control databases in 25 of 277226 chromosomes at a frequency of 0.0001 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 2 of 24032 chromosomes (freq: 0.0001), European in 23 of 126718 chromosomes (freq: 0.0002); it was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Ile14 variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. However, 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 27, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at