NM_000535.7(PMS2):c.1004A>T (p.Asn335Ile) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 4, 2021
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:: RCV001818398.4

Allele description [Variation Report for NM_000535.7(PMS2):c.1004A>T (p.Asn335Ile)]

NM_000535.7(PMS2):c.1004A>T (p.Asn335Ile)

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.1004A>T (p.Asn335Ile)

HGVS:

NC_000007.14:g.5989940T>A
NG_008466.1:g.24167A>T
NM_000535.7:c.1004A>TMANE SELECT
NM_001322003.2:c.599A>T
NM_001322004.2:c.599A>T
NM_001322005.2:c.599A>T
NM_001322006.2:c.988+2033A>T
NM_001322007.2:c.686A>T
NM_001322008.2:c.686A>T
NM_001322009.2:c.599A>T
NM_001322010.2:c.583+2033A>T
NM_001322011.2:c.71A>T
NM_001322012.2:c.71A>T
NM_001322013.2:c.431A>T
NM_001322014.2:c.1004A>T
NM_001322015.2:c.695A>T
NP_000526.2:p.Asn335Ile
NP_001308932.1:p.Asn200Ile
NP_001308933.1:p.Asn200Ile
NP_001308934.1:p.Asn200Ile
NP_001308936.1:p.Asn229Ile
NP_001308937.1:p.Asn229Ile
NP_001308938.1:p.Asn200Ile
NP_001308940.1:p.Asn24Ile
NP_001308941.1:p.Asn24Ile
NP_001308942.1:p.Asn144Ile
NP_001308943.1:p.Asn335Ile
NP_001308944.1:p.Asn232Ile
LRG_161t1:c.1004A>T
LRG_161:g.24167A>T
NC_000007.13:g.6029571T>A
NM_000535.5:c.1004A>T
NM_000535.6:c.1004A>T
NR_136154.1:n.1091A>T
p.N335I

Protein change:

N144I

Links:

dbSNP: rs200513014

NCBI 1000 Genomes Browser:

rs200513014

Molecular consequence:

NM_001322006.2:c.988+2033A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.583+2033A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.1004A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.599A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.599A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.599A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.686A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.686A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.599A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.71A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.71A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.431A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.1004A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.695A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.1091A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002069658	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 4, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002069658

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 4, 2021)

germline

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Genetic Services Laboratory, University of Chicago, SCV002069658.1

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

Description

DNA sequence analysis of the PMS2 gene demonstrated a sequence change, c.1004A>T, in exon 10 which results in an amino acid change, p.Asn335Ile. This sequence change has been described in the gnomAD database in one individual with an overall population frequency of 0.0004% (dbSNP rs200513014). The p.Asn335Ile change has been described in an individual with colorectal cancer (PMID: 28466842). Additionally, a different amino acid change at the same location (p.Asn335Ser) has been reported in association with breast and/or ovarian cancer (PMID: 24549055). The p.Asn335Ile change affects a highly conserved amino acid residue located in a domain of the PMS2 protein that is known to be functional. The p.Asn335Ile substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Asn335Ile change remains unknown at this time.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 20, 2024

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