NM_000535.7(PMS2):c.672G>C (p.Lys224Asn) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 30, 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:: RCV000574446.7

Allele description [Variation Report for NM_000535.7(PMS2):c.672G>C (p.Lys224Asn)]

NM_000535.7(PMS2):c.672G>C (p.Lys224Asn)

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.672G>C (p.Lys224Asn)

HGVS:

NC_000007.14:g.5999141C>G
NG_008466.1:g.14966G>C
NM_000535.7:c.672G>CMANE SELECT
NM_001322003.2:c.267G>C
NM_001322004.2:c.267G>C
NM_001322005.2:c.267G>C
NM_001322006.2:c.672G>C
NM_001322007.2:c.354G>C
NM_001322008.2:c.354G>C
NM_001322009.2:c.267G>C
NM_001322010.2:c.267G>C
NM_001322011.2:c.-262G>C
NM_001322012.2:c.-262G>C
NM_001322013.2:c.133-1718G>C
NM_001322014.2:c.672G>C
NM_001322015.2:c.363G>C
NP_000526.2:p.Lys224Asn
NP_001308932.1:p.Lys89Asn
NP_001308933.1:p.Lys89Asn
NP_001308934.1:p.Lys89Asn
NP_001308935.1:p.Lys224Asn
NP_001308936.1:p.Lys118Asn
NP_001308937.1:p.Lys118Asn
NP_001308938.1:p.Lys89Asn
NP_001308939.1:p.Lys89Asn
NP_001308943.1:p.Lys224Asn
NP_001308944.1:p.Lys121Asn
LRG_161t1:c.672G>C
LRG_161:g.14966G>C
NC_000007.13:g.6038772C>G
NM_000535.5:c.672G>C
NM_000535.6:c.672G>C
NR_136154.1:n.759G>C

Protein change:

K118N

Links:

dbSNP: rs748141595

NCBI 1000 Genomes Browser:

rs748141595

Molecular consequence:

NM_001322011.2:c.-262G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-262G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.133-1718G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.672G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.672G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.354G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.354G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.267G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.672G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.363G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.759G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

Clear Turn Off Turn On

ACSL3 [Anas platyrhynchos]
ACSL3 [Anas platyrhynchos]
Gene ID:101796118

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000670816	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 30, 2023)	germline	clinical testing	Citation Link,
SCV000691096	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 28, 2019)	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

SCV000670816

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 30, 2023)

germline

clinical testing

Citation Link,

SCV000691096

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 28, 2019)

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	unknown	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 Ambry Genetics, SCV000670816.5

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

Description

The p.K224N variant (also known as c.672G>C), located in coding exon 6 of the PMS2 gene, results from a G to C substitution at nucleotide position 672. The lysine at codon 224 is replaced by asparagine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000691096.3

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine