VCV000005723.2 - ClinVar

NM_194454.3(KRIT1):c.845+2T>C

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.

(2)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_194454.3(KRIT1):c.845+2T>C

Variation ID: 5723 Accession: VCV000005723.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 7q21.2 7: 92234806 (GRCh38) [ NCBI UCSC ] 7: 91864120 (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	Oct 21, 2016	Dec 2, 2023	Nov 24, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_194454.3:c.845+2T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_001013406.2:c.845+2T>C		splice donor
NM_001350669.1:c.845+2T>C		splice donor
NM_001350670.1:c.845+2T>C		splice donor
NM_001350671.1:c.131+2T>C		splice donor
NM_001350672.1:c.845+2T>C		splice donor
NM_001350673.1:c.845+2T>C		splice donor
NM_001350674.1:c.845+2T>C		splice donor
NM_001350675.1:c.845+2T>C		splice donor
NM_001350676.1:c.845+2T>C		splice donor
NM_001350677.1:c.845+2T>C		splice donor
NM_001350678.1:c.845+2T>C		splice donor
NM_001350679.1:c.845+2T>C		splice donor
NM_001350680.1:c.845+2T>C		splice donor
NM_001350681.1:c.845+2T>C		splice donor
NM_001350682.1:c.845+2T>C		splice donor
NM_001350683.1:c.845+2T>C		splice donor
NM_001350684.1:c.845+2T>C		splice donor
NM_001350685.1:c.845+2T>C		splice donor
NM_001350686.1:c.845+2T>C		splice donor
NM_001350687.1:c.845+2T>C		splice donor
NM_001350688.1:c.845+2T>C		splice donor
NM_001350689.1:c.845+2T>C		splice donor
NM_001350690.1:c.845+2T>C		splice donor
NM_001350691.1:c.845+2T>C		splice donor
NM_001350692.1:c.845+2T>C		splice donor
NM_001350693.1:c.845+2T>C		splice donor
NM_001350694.1:c.845+2T>C		splice donor
NM_001350695.1:c.845+2T>C		splice donor
NM_001350696.1:c.845+2T>C		splice donor
NM_001350697.1:c.845+2T>C		splice donor
NM_004912.4:c.845+2T>C		splice donor
NM_194455.1:c.845+2T>C		splice donor
NM_194456.1:c.845+2T>C		splice donor
NC_000007.14:g.92234806A>G
NC_000007.13:g.91864120A>G
NG_012964.1:g.16295T>C
LRG_650:g.16295T>C
LRG_650t1:c.845+2T>C

... more HGVS ... less HGVS

Protein change

Other names

IVS2DS, T-C, +2

Canonical SPDI

NC_000007.14:92234805:A:G

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.

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

Links

OMIM: 604214.0006 dbSNP: rs1563302930 VarSome

Comment on variant

NCBI staff provided an HGVS expression for allelic variant 604214.0006 based on the sequence reported in Figure 2 of the paper by Eerola et al., 2000 (PubMed 10814716). According to annotation of the RefSeqGene NG_012964.1, this location in the donor site of intron 10.

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.
KRIT1		-	-	GRCh38 GRCh37	658	688

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.
Cerebral cavernous malformation 1	Pathogenic (1)	no assertion criteria provided	May 22, 2000	RCV000006077.3
Cerebral cavernous malformation	Pathogenic (1)	no assertion criteria provided	Nov 24, 2023	RCV003444193.1

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.
Pathogenic (May 22, 2000)	no assertion criteria provided Method: literature only	CEREBRAL CAVERNOUS MALFORMATIONS 1 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000026259.2 First in ClinVar: Apr 04, 2013 Last updated: Oct 21, 2016	Publications: PubMed (1) PubMed: 10814716 Comment on evidence: Eerola et al. (2000) reported a 3-generation family with cerebral cavernous malformations (CCM1; 116860) in which affected members were heterozygous for a T-to-C transition in … (more) Eerola et al. (2000) reported a 3-generation family with cerebral cavernous malformations (CCM1; 116860) in which affected members were heterozygous for a T-to-C transition in the splice donor site of intron 2 of the KRIT1 gene. RT-PCR analysis of lymphoblastoid cells from affected individuals yielded aberrant cDNA products from the mutant allele that lacked either exon 2 or both exons 2 and 3. (less)
Pathogenic (Nov 24, 2023)	no assertion criteria provided Method: clinical testing	Cerebral cavernous malformation Affected status: yes Allele origin: germline	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas Accession: SCV004171614.1 First in ClinVar: Dec 02, 2023 Last updated: Dec 02, 2023

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
KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation.	Eerola I	Human molecular genetics	2000	PMID: 10814716

Text-mined citations for rs1563302930 ...

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 Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_194454.3(KRIT1):c.845+2T>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1563302930 ...