NM_000535.7(PMS2):c.1882C>T (p.Arg628Ter) AND Lynch syndrome 4

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Oct 12, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000009823.10

Allele description [Variation Report for NM_000535.7(PMS2):c.1882C>T (p.Arg628Ter)]

NM_000535.7(PMS2):c.1882C>T (p.Arg628Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.1882C>T (p.Arg628Ter)

HGVS:

NC_000007.14:g.5986883G>A
NG_008466.1:g.27224C>T
NM_000535.7:c.1882C>TMANE SELECT
NM_001322003.2:c.1477C>T
NM_001322004.2:c.1477C>T
NM_001322005.2:c.1477C>T
NM_001322006.2:c.1726C>T
NM_001322007.2:c.1564C>T
NM_001322008.2:c.1564C>T
NM_001322009.2:c.1477C>T
NM_001322010.2:c.1321C>T
NM_001322011.2:c.949C>T
NM_001322012.2:c.949C>T
NM_001322013.2:c.1309C>T
NM_001322014.2:c.1882C>T
NM_001322015.2:c.1573C>T
NP_000526.2:p.Arg628Ter
NP_001308932.1:p.Arg493Ter
NP_001308933.1:p.Arg493Ter
NP_001308934.1:p.Arg493Ter
NP_001308935.1:p.Arg576Ter
NP_001308936.1:p.Arg522Ter
NP_001308937.1:p.Arg522Ter
NP_001308938.1:p.Arg493Ter
NP_001308939.1:p.Arg441Ter
NP_001308940.1:p.Arg317Ter
NP_001308941.1:p.Arg317Ter
NP_001308942.1:p.Arg437Ter
NP_001308943.1:p.Arg628Ter
NP_001308944.1:p.Arg525Ter
LRG_161t1:c.1882C>T
LRG_161:g.27224C>T
NC_000007.13:g.6026514G>A
NM_000535.5:c.1882C>T
NM_000535.6:c.1882C>T
NR_136154.1:n.1969C>T

Protein change:

R317*; ARG628TER

Links:

OMIM: 600259.0009; dbSNP: rs63750451

NCBI 1000 Genomes Browser:

rs63750451

Molecular consequence:

NR_136154.1:n.1969C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.1882C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322003.2:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322004.2:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322005.2:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.1726C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322007.2:c.1564C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322008.2:c.1564C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322009.2:c.1477C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322010.2:c.1321C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322011.2:c.949C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322012.2:c.949C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322013.2:c.1309C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.1882C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322015.2:c.1573C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Lynch syndrome 4 (LYNCH4)
Synonyms:: Colorectal cancer, hereditary nonpolyposis, type 4; Hereditary non-polyposis colorectal cancer, type 4
Identifiers:: MONDO: MONDO:0013699; MedGen: C1838333; Orphanet: 144; OMIM: 614337

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000030044	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2006)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000734561	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV000745188	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Mar 16, 2016)	germline	clinical testing	Citation Link,
SCV004187756	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Sep 21, 2023)	unknown	clinical testing	Citation Link,
SCV004205394	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 12, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome).

Hendriks YM, Jagmohan-Changur S, van der Klift HM, Morreau H, van Puijenbroek M, Tops C, van Os T, Wagner A, Ausems MG, Gomez E, Breuning MH, Bröcker-Vriends AH, Vasen HF, Wijnen JT.

Gastroenterology. 2006 Feb;130(2):312-22.

PubMed [citation]

PMID:: 16472587

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000030044.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a family with hereditary nonpolyposis colorectal cancer (LYNCH4; 614337), Hendriks et al. (2006) identified heterozygosity for a 1882C-T transition in exon 11 of the PMS2 gene, predicted to result in an arg628-to-ter (R628X) substitution. The mutation cosegregated with disease.

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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000734561.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000745188.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Myriad Genetics, Inc., SCV004187756.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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

From Baylor Genetics, SCV004205394.1

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

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

Last Updated: Mar 16, 2024

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