rs1057517457
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001048174.2(MUTYH):c.442_451del(p.Gly148ThrfsTer16) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,066 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. G148G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001048174.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001048174.2 | c.442_451del | p.Gly148ThrfsTer16 | frameshift_variant | 7/16 | ENST00000456914.7 | |
MUTYH | NM_001128425.2 | c.526_535del | p.Gly176ThrfsTer16 | frameshift_variant | 7/16 | ENST00000710952.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000456914.7 | c.442_451del | p.Gly148ThrfsTer16 | frameshift_variant | 7/16 | 1 | NM_001048174.2 | A1 | |
MUTYH | ENST00000710952.2 | c.526_535del | p.Gly176ThrfsTer16 | frameshift_variant | 7/16 | NM_001128425.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461884Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727246
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 2 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 26, 2023 | This sequence change creates a premature translational stop signal (p.Gly176Thrfs*16) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686). This variant is not present in population databases (gnomAD no frequency). 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: 371677). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 11, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Feb 16, 2016 | - - |
Hereditary cancer-predisposing syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 25, 2021 | The c.526_535del10 pathogenic mutation, located in coding exon 7 of the MUTYH gene, results from a deletion of 10 nucleotides at nucleotide positions 526 to 535, causing a translational frameshift with a predicted alternate stop codon. This alteration was observed in the germline of an individual with a pancreatic neuroendocrine tumor (Scarpa A et al. Nature, 2017 Mar;543:65-71). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Pathogenic, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jan 15, 2020 | This variant deletes 10 nucleotides in exon 7 of the MUTYH gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Dec 04, 2018 | The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Not found in the total gnomAD dataset, and the data is high quality. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at