NM_000535.7(PMS2):c.79del (p.Cys27fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 20, 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:: RCV003099810.3

Allele description [Variation Report for NM_000535.7(PMS2):c.79del (p.Cys27fs)]

NM_000535.7(PMS2):c.79del (p.Cys27fs)

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.79del (p.Cys27fs)

HGVS:

NC_000007.14:g.6005978del
NG_008466.1:g.8131del
NG_050738.1:g.1728del
NM_000535.7:c.79delMANE SELECT
NM_001018040.1:c.-329delT
NM_001322003.2:c.-327del
NM_001322004.2:c.-242-1918del
NM_001322005.2:c.-327del
NM_001322006.2:c.79del
NM_001322007.2:c.-137del
NM_001322008.2:c.-52-1918del
NM_001322009.2:c.-327del
NM_001322010.2:c.-242-1918del
NM_001322011.2:c.-806del
NM_001322012.2:c.-806del
NM_001322013.2:c.-327del
NM_001322014.2:c.79del
NM_001322015.2:c.-406del
NM_001406866.1:c.263delT
NM_001406868.1:c.77delT
NM_001406869.1:c.77delT
NM_001406870.1:c.77delT
NM_001406871.1:c.77delT
NM_001406872.1:c.77delT
NM_001406873.1:c.77delT
NM_001406874.1:c.77delT
NM_001406875.1:c.-408delT
NM_001406876.1:c.-139delT
NM_001406877.1:c.-408delT
NM_001406878.1:c.-408delT
NM_001406880.1:c.-355delT
NM_001406882.1:c.-408delT
NM_001406883.1:c.-139delT
NM_001406884.1:c.77delT
NM_001406885.1:c.77delT
NM_001406886.1:c.77delT
NM_001406887.1:c.-329delT
NM_001406888.1:c.-276delT
NM_001406889.1:c.-276delT
NM_001406890.1:c.-319delT
NM_001406891.1:c.-329delT
NM_001406892.1:c.-276delT
NM_001406893.1:c.-329delT
NM_001406894.1:c.-276delT
NM_001406896.1:c.-139delT
NM_001406897.1:c.-329delT
NM_001406898.1:c.-329delT
NM_001406899.1:c.-276delT
NM_001406900.1:c.-305delT
NM_001406901.1:c.-139delT
NM_001406902.1:c.-139delT
NM_001406903.1:c.-139delT
NM_001406904.1:c.-276delT
NM_001406905.1:c.-329delT
NM_001406906.1:c.-329delT
NM_001406907.1:c.-276delT
NM_001406908.1:c.-329delT
NM_001406909.1:c.-276delT
NM_001406910.1:c.-329delT
NM_001406912.1:c.77delT
NP_000526.1:p.Cys27Alafs
NP_000526.2:p.Cys27fs
NP_001308935.1:p.Cys27fs
NP_001308943.1:p.Cys27fs
NP_001393795.1:p.Cys89Alafs
NP_001393797.1:p.Cys27Alafs
NP_001393798.1:p.Cys27Alafs
NP_001393799.1:p.Cys27Alafs
NP_001393800.1:p.Cys27Alafs
NP_001393801.1:p.Cys27Alafs
NP_001393802.1:p.Cys27Alafs
NP_001393803.1:p.Cys27Alafs
NP_001393813.1:p.Cys27Alafs
NP_001393814.1:p.Cys27Alafs
NP_001393815.1:p.Cys27Alafs
NP_001393841.1:p.Cys27Alafs
LRG_161t1:c.77del
LRG_161:g.8131del
LRG_161p1:p.Cys27Alafs
NC_000007.13:g.6045607del
NC_000007.13:g.6045609del
NM_000535.5:c.77delT
NM_000535.5:c.79delT
NR_003085.2:n.159delT
NR_136154.1:n.166del

Protein change:

C27fs

Molecular consequence:

NM_001322003.2:c.-327del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-327del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.-137del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-327del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-806del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-806del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-327del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-406del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000535.7:c.79del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322006.2:c.79del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322014.2:c.79del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406866.1:c.263delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406868.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406869.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406870.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406871.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406872.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406873.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406874.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406884.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406885.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406886.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406912.1:c.77delT - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322004.2:c.-242-1918del - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.-52-1918del - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.-242-1918del - intron variant - [Sequence Ontology: SO:0001627]
NR_136154.1:n.166del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV003196557	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 20, 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

SCV003196557

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 20, 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, SCV003196557.2

#	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.Cys27Alafs*7) 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: 1761572). 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: Sep 29, 2024

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