VCV000036692.40 - ClinVar

NM_000535.7(PMS2):c.705+17A>G

Germline

Top reviewed classifications are shown here.

Submission summary:

18 submissions

18 submitters

8 conditions

Reviewed by expert panel

No known pathogenicity

Sep 2013 by International …

for Lynch Syndrome

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000535.7(PMS2):c.705+17A>G

Variation ID: 36692 Accession: VCV000036692.40

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7p22.1 7: 5999091 (GRCh38) [ NCBI UCSC ] 7: 6038722 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	May 1, 2024	Sep 5, 2013

HGVS

Nucleotide	Protein	Molecular consequence
NM_000535.7:c.705+17A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001322003.2:c.300+17A>G		intron variant
NM_001322004.2:c.300+17A>G		intron variant
NM_001322005.2:c.300+17A>G		intron variant
NM_001322006.2:c.705+17A>G		intron variant
NM_001322007.2:c.387+17A>G		intron variant
NM_001322008.2:c.387+17A>G		intron variant
NM_001322009.2:c.300+17A>G		intron variant
NM_001322010.2:c.300+17A>G		intron variant
NM_001322011.2:c.-229+17A>G		intron variant
NM_001322012.2:c.-229+17A>G		intron variant
NM_001322013.2:c.133-1668A>G		intron variant
NM_001322014.2:c.705+17A>G		intron variant
NM_001322015.2:c.396+17A>G		intron variant
NC_000007.14:g.5999091T>C
NC_000007.13:g.6038722T>C
NG_008466.1:g.15016A>G
LRG_161:g.15016A>G
LRG_161t1:c.705+17A>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000007.14:5999090:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.32568 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.33782

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.34392

Exome Aggregation Consortium (ExAC) 0.36776

The Genome Aggregation Database (gnomAD), exomes 0.36821

1000 Genomes Project 30x 0.31902

1000 Genomes Project 0.32568

Trans-Omics for Precision Medicine (TOPMed) 0.33480

Links

ClinGen: CA012587 dbSNP: rs62456182 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PMS2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	5241	5343

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Lynch syndrome	Benign (2)	reviewed by expert panel	Sep 5, 2013	RCV000030371.14
Hereditary cancer-predisposing syndrome	Benign (2)	criteria provided, multiple submitters, no conflicts	Mar 31, 2015	RCV000130741.13
not specified	Benign (6)	criteria provided, multiple submitters, no conflicts	Aug 22, 2013	RCV000079110.28
Lynch syndrome 4	Benign (3)	criteria provided, multiple submitters, no conflicts	Jul 7, 2023	RCV000611694.11
Hereditary nonpolyposis colorectal neoplasms	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV001516745.15
Breast and/or ovarian cancer	Benign (1)	criteria provided, single submitter	Apr 21, 2021	RCV001798023.10
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Nov 29, 2023	RCV001707511.19
Mismatch repair cancer syndrome 4	Benign (1)	criteria provided, single submitter	Oct 25, 2021	RCV001788998.10

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
no known pathogenicity (Sep 05, 2013)	reviewed by expert panel (Guidelines v1.9) Method: research	Lynch Syndrome Affected status: unknown Allele origin: germline	International Society for Gastrointestinal Hereditary Tumours (InSiGHT) Accession: SCV000108377.3 First in ClinVar: Dec 19, 2013 Last updated: Dec 24, 2022 Comment: Classified with v1.9 guidelines: https://docs.google.com/file/d/0B3JL6rP6JzhoN2EydHRVMEI1UGs	Comments (2): MAF >1% Converted during submission to Benign.
Benign (Aug 22, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000110979.8 First in ClinVar: Jan 17, 2014 Last updated: Feb 19, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PMS2 Number of individuals with the variant: 28 Sex: mixed
Benign (Mar 31, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000537328.1 First in ClinVar: Aug 06, 2014 Last updated: Aug 06, 2014
Benign (Sep 21, 2015)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Lynch syndrome 4 Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV000745198.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000304737.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001934905.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (Oct 25, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Mismatch repair cancer syndrome 4 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002031511.1 First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021
Benign (Apr 21, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast and/or ovarian cancer Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV002042814.1 First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022
benign (Aug 18, 2011)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Hereditary non-polyposis colon cancer (autosomal unknown) Affected status: not provided Allele origin: not applicable	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000053038.2 First in ClinVar: Apr 04, 2013 Last updated: Apr 11, 2022	Publications: PubMed (3) PubMed: 16472587‚ 20205264‚ 14756672 Comment: Converted during submission to Benign.
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lynch syndrome 4 Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004016576.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary nonpolyposis colorectal neoplasms Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001725076.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 14, 2024
Benign (Nov 29, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000604898.9 First in ClinVar: Oct 02, 2016 Last updated: Feb 20, 2024
Benign (Sep 30, 2014)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000185632.6 First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024	Comment: 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 … (more) 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. (less)
Benign (-)	no assertion criteria provided Method: clinical testing	Lynch syndrome 4 Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000734567.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001906214.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001918444.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000691977.1 First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001957240.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

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.

Germline Functional Evidence

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical analysis of PMS2: mutation detection and avoidance of pseudogenes.	Vaughn CP	Human mutation	2010	PMID: 20205264
Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome).	Hendriks YM	Gastroenterology	2006	PMID: 16472587
Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations.	Thompson E	Clinical genetics	2004	PMID: 14756672
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PMS2	-	-	-	-
http://www.insight-database.org/classifications/index.html?gene=PMS2&variant=c.705%2B17A%3EG	-	-	-	-

Text-mined citations for rs62456182 ...

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 Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_000535.7(PMS2):c.705+17A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs62456182 ...