rs55954143
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000535.7(PMS2):c.2007-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,409,502 control chromosomes in the GnomAD database, including 4,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Consequence
NM_000535.7 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMS2 | NM_000535.7 | c.2007-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000265849.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMS2 | ENST00000265849.12 | c.2007-7C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000535.7 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.117 AC: 17653AN: 150504Hom.: 1379 Cov.: 31
GnomAD3 exomes AF: 0.0758 AC: 11269AN: 148764Hom.: 514 AF XY: 0.0743 AC XY: 5950AN XY: 80070
GnomAD4 exome AF: 0.0684 AC: 86153AN: 1258874Hom.: 3075 Cov.: 18 AF XY: 0.0688 AC XY: 43227AN XY: 628484
GnomAD4 genome ? AF: 0.117 AC: 17693AN: 150628Hom.: 1391 Cov.: 31 AF XY: 0.118 AC XY: 8655AN XY: 73644
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 21, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Lynch syndrome 4 Benign:5
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Counsyl | Jun 13, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | May 31, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 05, 2023 | This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. - |
Lynch syndrome Benign:2
Benign, no assertion criteria provided | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 27, 2013 | - - |
Benign, reviewed by expert panel | research | International Society for Gastrointestinal Hereditary Tumours (InSiGHT) | Sep 05, 2013 | MAF >1% - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 23, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 31, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 15, 2014 | This alteration is classified as 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. - |
Hereditary nonpolyposis colorectal neoplasms Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Endometrial carcinoma Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The PMS2 c.2007-7C>T variant was identified in 24 of 1372 proband chromosomes (frequency: 0.017) from individuals or families with Lynch syndrome, but was classified as a benign polymorphism (Hansen 2014, Hendriks 2006, Niessen 2009, Sheng 2010, van der Klift 2016). The variant was also identified in dbSNP (rs55954143) with benign allele, ClinVar 6x (classified as benign, reviewed by an expert panel), Genesight-COGR, Insight Colon Cancer Gene Variant Database (as benign), and Mismatch Repair Genes Variant Database. The variant was not identified in Cosmic, MutDB, Zhejiang Colon Cancer Database, MMR Gene Unclassified Variants Database, or Insight Hereditary Tumors Database. The variant was identified in control databases in 14684 of 174456 chromosomes (776 homozygous) at a frequency of 0.08 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was identified in the following populations at a frequency greater than 1%: African in 3950 of 15996 chromosomes (freq: 0.247), East Asian in 1045 of 11848 chromosomes (freq: 0.088), European (Finnish) in 1617 of 19226 chromosomes (freq: 0.084), South Asian in 1722 of 20892 chromosomes (freq: 0.082), Other in 326 of 4640 chromosomes (freq: 0.07), European (Non-Finnish) in 4958 of 72394 chromosomes (freq: 0.068), Ashkenazi Jewish* in 329 of 7828 chromosomes (freq: 0.042). In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at