NM_000535.7(PMS2):c.1970del (p.Asn657fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 23, 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:: RCV000810208.7

Allele description [Variation Report for NM_000535.7(PMS2):c.1970del (p.Asn657fs)]

NM_000535.7(PMS2):c.1970del (p.Asn657fs)

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.1970del (p.Asn657fs)

HGVS:

NC_000007.14:g.5986798del
NG_008466.1:g.27312del
NM_000535.7:c.1970delMANE SELECT
NM_001322003.2:c.1565del
NM_001322004.2:c.1565del
NM_001322005.2:c.1565del
NM_001322006.2:c.1814del
NM_001322007.2:c.1652del
NM_001322008.2:c.1652del
NM_001322009.2:c.1565del
NM_001322010.2:c.1409del
NM_001322011.2:c.1037del
NM_001322012.2:c.1037del
NM_001322013.2:c.1397del
NM_001322014.2:c.1970del
NM_001322015.2:c.1661del
NP_000526.2:p.Asn657fs
NP_001308932.1:p.Asn522fs
NP_001308933.1:p.Asn522fs
NP_001308934.1:p.Asn522fs
NP_001308935.1:p.Asn605fs
NP_001308936.1:p.Asn551fs
NP_001308937.1:p.Asn551fs
NP_001308938.1:p.Asn522fs
NP_001308939.1:p.Asn470fs
NP_001308940.1:p.Asn346fs
NP_001308941.1:p.Asn346fs
NP_001308942.1:p.Asn466fs
NP_001308943.1:p.Asn657fs
NP_001308944.1:p.Asn554fs
LRG_161t1:c.1970del
LRG_161:g.27312del
NC_000007.13:g.6026426del
NC_000007.13:g.6026429del
NM_000535.5:c.1970del
NM_000535.5:c.1970delA
NM_000535.6:c.1970del
NR_136154.1:n.2057del

Protein change:

N346fs

Links:

dbSNP: rs1064794566

NCBI 1000 Genomes Browser:

rs1064794566

Molecular consequence:

NM_000535.7:c.1970del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322003.2:c.1565del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322004.2:c.1565del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322005.2:c.1565del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322006.2:c.1814del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322007.2:c.1652del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322008.2:c.1652del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322009.2:c.1565del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322010.2:c.1409del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322011.2:c.1037del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322012.2:c.1037del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322013.2:c.1397del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322014.2:c.1970del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322015.2:c.1661del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_136154.1:n.2057del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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transmembrane protein 196 [Homo sapiens]
transmembrane protein 196 [Homo sapiens]
gi|61098058|ref|NP_689987.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000950401	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 23, 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

SCV000950401

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 23, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000950401.6

#	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.Asn657Ilefs*8) 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. ClinVar contains an entry for this variant (Variation ID: 496034). 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: Sep 29, 2024

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