NM_000061.3(BTK):c.1751-1G>T AND X-linked agammaglobulinemia with growth hormone deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 4, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003513681.2

Allele description [Variation Report for NM_000061.3(BTK):c.1751-1G>T]

NM_000061.3(BTK):c.1751-1G>T

Gene:

BTK:Bruton tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_000061.3(BTK):c.1751-1G>T

HGVS:

NC_000023.11:g.101353352C>A
NG_009616.1:g.37873G>T
NG_011734.1:g.618G>T
NM_000061.3:c.1751-1G>TMANE SELECT
NM_001287344.2:c.1853-1G>T
NM_001287345.2:c.1223-1G>T
LRG_128:g.37873G>T
NC_000023.10:g.100608340C>A

Molecular consequence:

NM_000061.3:c.1751-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001287344.2:c.1853-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001287345.2:c.1223-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: X-linked agammaglobulinemia with growth hormone deficiency (IGHD3)
Synonyms:: IGHD III; Isolated growth hormone deficiency type 3; Growth hormone deficiency with hypogammaglobulinemia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010615; MedGen: C0472813; Orphanet: 631; OMIM: 307200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004300155	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 4, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9106525, 16712653, 16199547, 15661032, 16862044, 19419768, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004300155

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 4, 2022)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Unusual patterns of exon skipping in Bruton tyrosine kinase are associated with mutations involving the intron 17 3' splice site.

Haire RN, Ohta Y, Strong SJ, Litman RT, Liu Y, Prchal JT, Cooper MD, Litman GW.

Am J Hum Genet. 1997 Apr;60(4):798-807.

PubMed [citation]

PMID:: 9106525
PMCID:: PMC1712487

Identification of Bruton tyrosine kinase mutations in 12 Chinese patients with X-linked agammaglobulinaemia by long PCR-direct sequencing.

Chan KW, Chen T, Jiang L, Fok SF, Lee TL, Lee BW, Yang X, Lau YL.

Int J Immunogenet. 2006 Jun;33(3):205-9.

PubMed [citation]

PMID:: 16712653

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004300155.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (PMID: 9106525). Disruption of this splice site has been observed in individuals with agammaglobulinemia (PMID: 9106525, 16712653; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 17 of the BTK gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BTK are known to be pathogenic (PMID: 15661032, 16862044, 19419768).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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