VCV000135065.29 - ClinVar

NM_000535.7(PMS2):c.1621A>G (p.Lys541Glu)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(16)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000535.7(PMS2):c.1621A>G (p.Lys541Glu)

Variation ID: 135065 Accession: VCV000135065.29

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7p22.1 7: 5987144 (GRCh38) [ NCBI UCSC ] 7: 6026775 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 9, 2014	Apr 20, 2024	Feb 5, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000535.7:c.1621A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000526.2:p.Lys541Glu	missense
NM_001322003.2:c.1216A>G	NP_001308932.1:p.Lys406Glu	missense
NM_001322004.2:c.1216A>G	NP_001308933.1:p.Lys406Glu	missense
NM_001322005.2:c.1216A>G	NP_001308934.1:p.Lys406Glu	missense
NM_001322006.2:c.1465A>G	NP_001308935.1:p.Lys489Glu	missense
NM_001322007.2:c.1303A>G	NP_001308936.1:p.Lys435Glu	missense
NM_001322008.2:c.1303A>G	NP_001308937.1:p.Lys435Glu	missense
NM_001322009.2:c.1216A>G	NP_001308938.1:p.Lys406Glu	missense
NM_001322010.2:c.1060A>G	NP_001308939.1:p.Lys354Glu	missense
NM_001322011.2:c.688A>G	NP_001308940.1:p.Lys230Glu	missense
NM_001322012.2:c.688A>G	NP_001308941.1:p.Lys230Glu	missense
NM_001322013.2:c.1048A>G	NP_001308942.1:p.Lys350Glu	missense
NM_001322014.2:c.1621A>G	NP_001308943.1:p.Lys541Glu	missense
NM_001322015.2:c.1312A>G	NP_001308944.1:p.Lys438Glu	missense
NR_136154.1:n.1708A>G		non-coding transcript variant
NC_000007.14:g.5987144T>C
NC_000007.13:g.6026775T>C
NG_008466.1:g.26963=
LRG_161:g.26963=
LRG_161t1:c.1621=
	P54278:p.Lys541Glu

... more HGVS ... less HGVS

Protein change

K541E, K406E, K354E, K438E, K489E, K230E, K350E, K435E

Other names

Canonical SPDI

NC_000007.14:5987143:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.11681 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.84078

Exome Aggregation Consortium (ExAC) 0.85139

Trans-Omics for Precision Medicine (TOPMed) 0.85886

The Genome Aggregation Database (gnomAD) 0.86482

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.87038

1000 Genomes Project 30x 0.87976

1000 Genomes Project 0.88319

Links

ClinGen: CA044701 UniProtKB: P54278#VAR_024541 dbSNP: rs2228006 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PMS2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	5243	5345

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (10)	criteria provided, multiple submitters, no conflicts	Feb 5, 2018	RCV000121840.21
Lynch syndrome 4	Benign (3)	criteria provided, multiple submitters, no conflicts	Jul 7, 2023	RCV000515611.4
Hereditary nonpolyposis colorectal neoplasms	Benign (1)	criteria provided, single submitter	Feb 1, 2024	RCV000860105.9
Mismatch repair cancer syndrome 4	Benign (1)	criteria provided, single submitter	Oct 25, 2021	RCV001789176.2
Lynch syndrome	Benign (1)	criteria provided, single submitter	Feb 5, 2024	RCV003997355.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Oct 11, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000806183.1 First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018
Benign (Feb 05, 2018)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000203315.4 First in ClinVar: Jan 30, 2015 Last updated: Feb 19, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PMS2 Number of individuals with the variant: 159 Zygosity: Homozygote, Single Heterozygote Sex: mixed
Benign (Mar 28, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000540064.3 First in ClinVar: Mar 24, 2015 Last updated: Feb 19, 2018	Comment: Disclaimer: This variant has not undergone full assessment. The following are pr eliminary notes: Frequency Number of individuals with the variant: 2
Benign (Oct 25, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Mismatch repair cancer syndrome 4 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002031507.1 First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary nonpolyposis colorectal neoplasms Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001000028.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 28, 2024
Benign (Aug 18, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lynch syndrome 4 Affected status: no Allele origin: germline	IntelligeneCG Accession: SCV000611717.1 First in ClinVar: Dec 01, 2017 Last updated: Dec 01, 2017
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Lynch syndrome 4 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001137291.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Jul 07, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lynch syndrome 4 Affected status: yes Allele origin: germline	KCCC/NGS Laboratory, Kuwait Cancer Control Center Accession: SCV004016572.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023
Benign (Feb 05, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Lynch syndrome (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004844170.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Number of individuals with the variant: 103556 Zygosity: Homozygote, Single Heterozygote
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000691969.1 First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001740741.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001905868.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001922693.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001931153.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: unknown	Department of Pathology and Laboratory Medicine, Sinai Health System Additional submitter: Franklin by Genoox Study: The Canadian Open Genetics Repository (COGR) Accession: SCV001551099.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000086038.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation 1: Ethnicity/Population group: Whole_cohort Observation 2: Ethnicity/Population group: African Observation 3: Ethnicity/Population group: African_European Observation 4: Ethnicity/Population group: Central_Asian Observation 5: Ethnicity/Population group: East_Asian Observation 6: Ethnicity/Population group: European Observation 7: Ethnicity/Population group: Hispanic
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Germline Functional Evidence

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 germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PMS2	-	-	-	-

Text-mined citations for rs2228006 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000535.7(PMS2):c.1621A>G (p.Lys541Glu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2228006 ...