VCV000012036.1 - ClinVar

NM_000892.5(KLKB1):c.367G>A (p.Gly123Arg)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

This classification is based on the single submission received

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000892.5(KLKB1):c.367G>A (p.Gly123Arg)

Variation ID: 12036 Accession: VCV000012036.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 4q35.2 4: 186236819 (GRCh38) [ NCBI UCSC ] 4: 187157973 (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	Apr 4, 2013	Apr 4, 2013	Jul 1, 2007

HGVS

Nucleotide	Protein	Molecular consequence
NM_000892.5:c.367G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000883.2:p.Gly123Arg	missense
NM_001318394.2:c.253G>A	NP_001305323.1:p.Gly85Arg	missense
NM_001318396.2:c.-271G>A		5 prime UTR
NC_000004.12:g.186236819G>A
NC_000004.11:g.187157973G>A
NG_012095.2:g.32841G>A
LRG_565:g.32841G>A
LRG_565t1:c.367G>A	LRG_565p1:p.Gly123Arg

... more HGVS ... less HGVS

Protein change

G123R, G85R

Other names

G104R

Canonical SPDI

NC_000004.12:186236818:G:A

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.

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

Links

dbSNP: rs121964952 ClinGen: CA121833 OMIM: 229000.0004 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.
KLKB1		-	-	GRCh38 GRCh37	160	383

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.
Prekallikrein deficiency	Pathogenic (1)	no assertion criteria provided	Jul 1, 2007	RCV000012816.22

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.	Expand all rows Collapse all rows 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.
Pathogenic (Jul 01, 2007) C Contributing to aggregate classification	no assertion criteria provided	PREKALLIKREIN DEFICIENCY	OMIM Accession: SCV000033056.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (1) PubMed: 17598838 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In 3 members of a Japanese family with plasma prekallikrein deficiency (612423), Katsuda et al. (2007) identified homozygosity for 2 mutations in exon 5 of … (more) In 3 members of a Japanese family with plasma prekallikrein deficiency (612423), Katsuda et al. (2007) identified homozygosity for 2 mutations in exon 5 of the KLKB1 gene: a 438G-A transition resulting in a gly104-to-arg (G104R) substitution, and a 499A-G transition resulting in an asn124-to-ser (N124S) substitution (229000.0005). Both substitutions occurred in the A2 domain of the heavy chain. The authors designated this mutation PKD Seki. Using mutant A2 proteins in E. coli, Katsuda et al. (2007) demonstrated that the 2 substitutions in the A2 domain reduce the binding activity of A2 to high molecular weight kininogen, suggesting that this binding may play a crucial role in the first step of blood coagulation. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A new type of plasma prekallikrein deficiency associated with homozygosity for Gly104Arg and Asn124Ser in apple domain 2 of the heavy-chain region.	Katsuda I	European journal of haematology	2007	PMID: 17598838

Text-mined citations for rs121964952 ...

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 Apr 25, 2022