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NM_000535.7(PMS2):c.1828A>G (p.Lys610Glu)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
5 (Most recent: Sep 28, 2021)
Last evaluated:
Jul 8, 2021
Accession:
VCV000188287.16
Variation ID:
188287
Description:
single nucleotide variant
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NM_000535.7(PMS2):c.1828A>G (p.Lys610Glu)

Allele ID
186080
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
7p22.1
Genomic location
7: 5986937 (GRCh38) GRCh38 UCSC
7: 6026568 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_161:g.27170A>G
LRG_161t1:c.1828A>G
NC_000007.13:g.6026568T>C
... more HGVS
Protein change
K610E, K299E, K423E, K475E, K507E, K419E, K558E, K504E
Other names
-
Canonical SPDI
NC_000007.14:5986936:T:C
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (C)

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00004
1000 Genomes Project 0.00020
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00004
The Genome Aggregation Database (gnomAD), exomes 0.00003
The Genome Aggregation Database (gnomAD) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
Links
ClinGen: CA010309
dbSNP: rs199700509
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Jul 8, 2021 RCV000486825.5
Uncertain significance 1 criteria provided, single submitter Oct 1, 2020 RCV000168273.9
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jun 26, 2019 RCV000574365.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PMS2 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3086 3151

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jun 26, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000663448.3
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The p.K610E variant (also known as c.1828A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide … (more)
Likely benign
(Jul 15, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000902934.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Oct 01, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000218945.10
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (2)
Comment:
This sequence change replaces lysine with glutamic acid at codon 610 of the PMS2 protein (p.Lys610Glu). The lysine residue is weakly conserved and there is … (more)
Uncertain significance
(Jul 08, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000567198.6
Submitted: (Sep 28, 2021)
Evidence details
Comment:
Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed … (more)
Uncertain significance
(May 01, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV001155028.7
Submitted: (Jul 04, 2021)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Patterns and functional implications of rare germline variants across 12 cancer types. Lu C Nature communications 2015 PMID: 26689913

Text-mined citations for rs199700509...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021