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NM_000535.7(PMS2):c.1621= (p.Lys541=)

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Interpretation:
Benign​

Review status:
reviewed by expert panel
Submissions:
7 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 5, 2013
Accession:
VCV000036686.5
Variation ID:
36686
Description:
single nucleotide variant
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NM_000535.7(PMS2):c.1621= (p.Lys541=)

Allele ID
45347
Variant type
single nucleotide variant
Variant length
-
Cytogenetic location
7p22.1
Genomic location
7: 5987144 (GRCh38) GRCh38 UCSC
7: 6026775 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000007.13:g.6026775=
NC_000007.14:g.5987144=
NM_000535.7:c.1621= MANE Select NP_000526.2:p.Lys541=
... more HGVS
Protein change
-
Other names
p.E541K:GAA>AAA
Canonical SPDI
NC_000007.14:5987143:T:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.11681 (T)

Allele frequency
Exome Aggregation Consortium (ExAC) 0.14861
Trans-Omics for Precision Medicine (TOPMed) 0.13204
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.12962
1000 Genomes Project 0.11681
The Genome Aggregation Database (gnomAD), exomes 0.15922
The Genome Aggregation Database (gnomAD) 0.12762
Links
ClinGen: CA009929
dbSNP: rs2228006
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Benign 2 reviewed by expert panel Sep 5, 2013 RCV000030365.4
Benign 2 criteria provided, multiple submitters, no conflicts Jan 28, 2015 RCV000212862.2
Benign 1 criteria provided, single submitter Dec 8, 2020 RCV001081089.2
Benign 1 criteria provided, single submitter Sep 1, 2020 RCV001282132.1
Benign 1 no assertion criteria provided Jul 13, 2012 RCV000034619.7
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PMS2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3062 3127

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
no known pathogenicity
(Sep 05, 2013)
reviewed by expert panel
Method: research
Lynch Syndrome
Allele origin: germline
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)
Accession: SCV000108304.2
Submitted: (Dec 18, 2013)
Comment:
Classified with v1.9 guidelines: https://docs.google.com/file/d/0B3JL6rP6JzhoN2EydHRVMEI1UGs
Evidence details
Comments (2):
MAF >1%
Converted during submission to Benign.
Benign
(Jan 28, 2015)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Department of Pathology and Laboratory Medicine,Sinai Health System
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000592937.1
Submitted: (Apr 19, 2017)
Evidence details
Publications
PubMed (8)
Benign
(Sep 01, 2020)
criteria provided, single submitter
Method: clinical testing
none provided
Allele origin: germline
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories
Accession: SCV000604900.3
Submitted: (Dec 11, 2020)
Evidence details
benign
(Aug 18, 2011)
criteria provided, single submitter
Method: clinical testing
Hereditary non-polyposis colon cancer
(autosomal unknown)
Allele origin: not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000053032.2
Submitted: (Aug 18, 2011)
Evidence details
Comment:
Converted during submission to Benign.
Benign
(Sep 10, 2013)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000171031.10
Submitted: (Mar 26, 2018)
Evidence details
Comment:
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 … (more)
Benign
(Dec 08, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000262462.7
Submitted: (Jan 07, 2021)
Evidence details
no known pathogenicity
(Jul 13, 2012)
no assertion criteria provided
Method: research
not provided
Allele origin: germline
Biesecker Lab/Clinical Genomics Section,National Institutes of Health
Study: ClinSeq
Accession: SCV000043425.1
Submitted: (Jul 15, 2012)
Evidence details
Publications
PubMed (1)
Comment:
Converted during submission to Benign.

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes. Hansen MF Molecular genetics & genomic medicine 2014 PMID: 24689082
Germline mutation and protein expression analysis of mismatch repair genes MSH6 and PMS2 in Malaysian Lynch syndrome patients. Zahary MN International journal of colorectal disease 2014 PMID: 24072394
Inactivation of DNA mismatch repair by variants of uncertain significance in the PMS2 gene. Drost M Human mutation 2013 PMID: 24027009
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Johnston JJ American journal of human genetics 2012 PMID: 22703879
Functional PMS2 hybrid alleles containing a pseudogene-specific missense variant trace back to a single ancient intrachromosomal recombination event. Ganster C Human mutation 2010 PMID: 20186689
Common variants in mismatch repair genes and risk of invasive ovarian cancer. Song H Carcinogenesis 2006 PMID: 16774946
Long-range PCR facilitates the identification of PMS2-specific mutations. Clendenning M Human mutation 2006 PMID: 16619239
Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome). Hendriks YM Gastroenterology 2006 PMID: 16472587
Mismatch repair gene PMS2: disease-causing germline mutations are frequent in patients whose tumors stain negative for PMS2 protein, but paralogous genes obscure mutation detection and interpretation. Nakagawa H Cancer research 2004 PMID: 15256438
Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations. Thompson E Clinical genetics 2004 PMID: 14756672
Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer. Viel A Genes, chromosomes & cancer 1997 PMID: 8993976
http://www.insight-database.org/classifications/index.html?gene=PMS2&variant=c.1621G%3EA - - - -

Text-mined citations for rs2228006...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 14, 2021