rs752666485
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000535.7(PMS2):c.1398C>T(p.Gly466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,012 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G466G) has been classified as Likely benign.
Frequency
Consequence
NM_000535.7 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMS2 | NM_000535.7 | c.1398C>T | p.Gly466= | synonymous_variant | 11/15 | ENST00000265849.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMS2 | ENST00000265849.12 | c.1398C>T | p.Gly466= | synonymous_variant | 11/15 | 1 | NM_000535.7 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251486Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135916
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461860Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 8AN XY: 727236
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
Lynch syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Sep 17, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | University of Washington Department of Laboratory Medicine, University of Washington | May 01, 2018 | PMS2 NM_000535.5:c.1398C>T has a 0.9% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.16 to 1, generated from evidence of seeing this as a somatic mutation in a tumor with loss of heterozygosity at the PMS2 locus. See Shirts et al 2018, PMID 29887214. - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 22, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2015 | 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 06, 2017 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | PMS2: BP4, BP7 - |
Hereditary nonpolyposis colorectal neoplasms Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at