NM_000061.3(BTK):c.1773C>A (p.Tyr591Ter) AND X-linked agammaglobulinemia with growth hormone deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 14, 2023
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:: RCV003511979.2

Allele description [Variation Report for NM_000061.3(BTK):c.1773C>A (p.Tyr591Ter)]

NM_000061.3(BTK):c.1773C>A (p.Tyr591Ter)

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.1773C>A (p.Tyr591Ter)

HGVS:

NC_000023.11:g.101353329G>T
NG_009616.1:g.37896C>A
NG_011734.1:g.641C>A
NM_000061.3:c.1773C>AMANE SELECT
NM_001287344.2:c.1875C>A
NM_001287345.2:c.1245C>A
NP_000052.1:p.Tyr591Ter
NP_000052.1:p.Tyr591Ter
NP_001274273.1:p.Tyr625Ter
NP_001274274.1:p.Tyr415Ter
LRG_128t1:c.1773C>A
LRG_128:g.37896C>A
LRG_128p1:p.Tyr591Ter
NC_000023.10:g.100608317G>T
NM_000061.2:c.1773C>A

Protein change:

Y415*; TYR591TER

Links:

OMIM: 300300.0045; dbSNP: rs128621207

NCBI 1000 Genomes Browser:

rs128621207

Molecular consequence:

NM_000061.3:c.1773C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001287344.2:c.1875C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001287345.2:c.1245C>A - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

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acetylcholine receptor subunit alpha-like [Amphiprion ocellaris]
acetylcholine receptor subunit alpha-like [Amphiprion ocellaris]
gi|1308428967|ref|XP_023135032.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004300153	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 14, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15661032, 16862044, 19419768, 7849697, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004300153

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 14, 2023)

germline

clinical testing

PubMed (5)
[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

Genetic analysis of patients with defects in early B-cell development.

Conley ME, Broides A, Hernandez-Trujillo V, Howard V, Kanegane H, Miyawaki T, Shurtleff SA.

Immunol Rev. 2005 Feb;203:216-34. Review.

PubMed [citation]

PMID:: 15661032

X-linked agammaglobulinemia: report on a United States registry of 201 patients.

Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, Conley ME, Cunningham-Rundles C, Ochs HD.

Medicine (Baltimore). 2006 Jul;85(4):193-202. doi: 10.1097/01.md.0000229482.27398.ad.

PubMed [citation]

PMID:: 16862044

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004300153.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Tyr591*) in the BTK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BTK are known to be pathogenic (PMID: 15661032, 16862044, 19419768). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked recessive agammaglobulinemia (PMID: 7849697). ClinVar contains an entry for this variant (Variation ID: 11386). For these reasons, this variant has been classified as Pathogenic.

#	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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