NM_000535.7(PMS2):c.537+1del AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 14, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001223326.7

Allele description [Variation Report for NM_000535.7(PMS2):c.537+1del]

NM_000535.7(PMS2):c.537+1del

Gene:

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.537+1del

HGVS:

NC_000007.14:g.6002453del
NG_008466.1:g.11655del
NM_000535.7:c.537+1delMANE SELECT
NM_001322003.2:c.132+1del
NM_001322004.2:c.132+1del
NM_001322005.2:c.132+1del
NM_001322006.2:c.537+1del
NM_001322007.2:c.219+1del
NM_001322008.2:c.219+1del
NM_001322009.2:c.132+1del
NM_001322010.2:c.132+1del
NM_001322011.2:c.-348+1del
NM_001322012.2:c.-348+1del
NM_001322013.2:c.132+1del
NM_001322014.2:c.537+1del
NM_001322015.2:c.228+1del
NM_001406866.1:c.723+1del
NM_001406868.1:c.561+1del
NM_001406869.1:c.537+1del
NM_001406870.1:c.537+1del
NM_001406871.1:c.537+1del
NM_001406872.1:c.537+1del
NM_001406873.1:c.537+1del
NM_001406874.1:c.537+1del
NM_001406875.1:c.228+1del
NM_001406876.1:c.219+1del
NM_001406877.1:c.228+1del
NM_001406878.1:c.228+1del
NM_001406879.1:c.228+1del
NM_001406880.1:c.228+1del
NM_001406881.1:c.228+1del
NM_001406882.1:c.228+1del
NM_001406883.1:c.219+1del
NM_001406884.1:c.537+1del
NM_001406885.1:c.250+1520del
NM_001406886.1:c.537+1del
NM_001406887.1:c.132+1del
NM_001406888.1:c.132+1del
NM_001406889.1:c.132+1del
NM_001406890.1:c.132+1del
NM_001406891.1:c.132+1del
NM_001406892.1:c.132+1del
NM_001406893.1:c.132+1del
NM_001406894.1:c.132+1del
NM_001406895.1:c.132+1del
NM_001406896.1:c.132+1del
NM_001406897.1:c.132+1del
NM_001406898.1:c.132+1del
NM_001406899.1:c.132+1del
NM_001406900.1:c.228+1del
NM_001406901.1:c.219+1del
NM_001406902.1:c.219+1del
NM_001406903.1:c.219+1del
NM_001406904.1:c.132+1del
NM_001406905.1:c.132+1del
NM_001406906.1:c.132+1del
NM_001406907.1:c.132+1del
NM_001406908.1:c.132+1del
NM_001406909.1:c.132+1del
NM_001406910.1:c.132+1del
NM_001406911.1:c.132+1del
NM_001406912.1:c.537+1del
LRG_161t1:c.537+1del
LRG_161:g.11655del
NC_000007.13:g.6042083del
NC_000007.13:g.6042084del
NM_000535.5:c.537+1del
NM_000535.5:c.537+1delG
NM_000535.6:c.537+1delG

Links:

dbSNP: rs1064793868

NCBI 1000 Genomes Browser:

rs1064793868

Molecular consequence:

NM_001406885.1:c.250+1520del - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322003.2:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322004.2:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322005.2:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322006.2:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322007.2:c.219+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322008.2:c.219+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322009.2:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322010.2:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322011.2:c.-348+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322012.2:c.-348+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322013.2:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322014.2:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001322015.2:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406866.1:c.723+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406868.1:c.561+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406869.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406870.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406871.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406872.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406873.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406874.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406875.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406876.1:c.219+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406877.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406878.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406879.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406880.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406881.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406882.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406883.1:c.219+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406884.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406886.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406887.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406888.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406889.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406890.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406891.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406892.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406893.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406894.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406895.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406896.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406897.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406898.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406899.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406900.1:c.228+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406901.1:c.219+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406902.1:c.219+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406903.1:c.219+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406904.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406905.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406906.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406907.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406908.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406909.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406910.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406911.1:c.132+1del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406912.1:c.537+1del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001395468	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21376568, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001395468

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines.

Herkert JC, Niessen RC, Olderode-Berends MJ, Veenstra-Knol HE, Vos YJ, van der Klift HM, Scheenstra R, Tops CM, Karrenbeld A, Peters FT, Hofstra RM, Kleibeuker JH, Sijmons RH.

Eur J Cancer. 2011 May;47(7):965-82. doi: 10.1016/j.ejca.2011.01.013. Epub 2011 Mar 4. Review.

PubMed [citation]

PMID:: 21376568

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]

PMID:: 24362816
PMCID:: PMC4294709

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001395468.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Glu180Serfs*21) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is also known as c.537+1del. ClinVar contains an entry for this variant (Variation ID: 419435). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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