VCV000011391.2 - ClinVar

NM_000061.3(BTK):c.1908_1909insTTTTAG (p.Lys637delinsPheTer)

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.

(1)

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_000061.3(BTK):c.1908_1909insTTTTAG (p.Lys637delinsPheTer)

Variation ID: 11391 Accession: VCV000011391.2

Type and length

Insertion, -

Location

Cytogenetic: Xq21.3-q22 -

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	Nov 3, 2018	Nov 3, 2018	Oct 29, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NM_000061.3:c.1908_1909insTTTTAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000052.1:p.Lys637delinsPheTer	nonsense
NM_001287344.2:c.2010_2011insTTTTAG	NP_001274273.1:p.Lys671delinsPheTer	nonsense
NM_001287345.2:c.1380_1381insTTTTAG	NP_001274274.1:p.Lys461delinsPheTer	nonsense
NC_000023.11:g.101353195_101353196insAAAACT
NC_000023.10:g.100608183_100608184insAAAACT
NG_009616.1:g.38031_38032insTTTTAG
NG_011734.1:g.776_777insTTTTAG
LRG_128:g.38031_38032insTTTTAG

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

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: 300300.0050 dbSNP: rs2147423959

Comment on variant

The genomic location for this variant will not be computed from alignment of the transcript sequence to the genome until there is experimental evidence for the genomic basis of the insertion at a splice junction.

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.
BTK		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	718	897

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.
X-linked agammaglobulinemia	Pathogenic (1)	no assertion criteria provided	Oct 29, 2018	RCV000012144.13

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 (Oct 29, 2018)	no assertion criteria provided Method: literature only	AGAMMAGLOBULINEMIA, X-LINKED Affected status: not provided Allele origin: germline	OMIM Accession: SCV000032378.2 First in ClinVar: Apr 04, 2013 Last updated: Nov 03, 2018	Publications: PubMed (1) PubMed: 7678697 Comment on evidence: In a patient with X-linked agammaglobulinemia (XLA; 300755), de Weers et al. (1994) identified a 6-bp (TTTTAG) insertion at position A2041 in the C-terminal region … (more) In a patient with X-linked agammaglobulinemia (XLA; 300755), de Weers et al. (1994) identified a 6-bp (TTTTAG) insertion at position A2041 in the C-terminal region of the BTK gene, resulting in a frameshift and a truncated protein. (less)

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
Human genetics. Becoming B cells.	Desiderio S	Nature	1993	PMID: 7678697

Text-mined citations for rs2147423959 ...

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_000061.3(BTK):c.1908_1909insTTTTAG (p.Lys637delinsPheTer)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2147423959 ...