NM_000061.3(BTK):c.1864G>C (p.Ala622Pro) AND X-linked agammaglobulinemia with growth hormone deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 5, 2020
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:: RCV001368905.7

Allele description [Variation Report for NM_000061.3(BTK):c.1864G>C (p.Ala622Pro)]

NM_000061.3(BTK):c.1864G>C (p.Ala622Pro)

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.1864G>C (p.Ala622Pro)

HGVS:

NC_000023.11:g.101353238C>G
NG_009616.1:g.37987G>C
NG_011734.1:g.732G>C
NM_000061.3:c.1864G>CMANE SELECT
NM_001287344.2:c.1966G>C
NM_001287345.2:c.1336G>C
NP_000052.1:p.Ala622Pro
NP_001274273.1:p.Ala656Pro
NP_001274274.1:p.Ala446Pro
LRG_128:g.37987G>C
NC_000023.10:g.100608226C>G

Protein change:

A446P

Links:

dbSNP: rs2147424035

NCBI 1000 Genomes Browser:

rs2147424035

Molecular consequence:

NM_000061.3:c.1864G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287344.2:c.1966G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287345.2:c.1336G>C - missense variant - [Sequence Ontology: SO:0001583]

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

Clear Turn Off Turn On

NADP-dependent oxidoreductase [Planococcus maritimus]
NADP-dependent oxidoreductase [Planococcus maritimus]
gi|1883792425|gnl|PRJNA647597|H1Q58 5|gb|QMT18191.1|

Protein
LOC135216677 [Macrobrachium nipponense]
LOC135216677 [Macrobrachium nipponense]
Gene ID:135216677

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001565324	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 5, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8938104, 9545398, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001565324

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 5, 2020)

germline

clinical testing

PubMed (3)
[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

Neutropenia in X-linked agammaglobulinemia.

Farrar JE, Rohrer J, Conley ME.

Clin Immunol Immunopathol. 1996 Dec;81(3):271-6.

PubMed [citation]

PMID:: 8938104

Mutations in btk in patients with presumed X-linked agammaglobulinemia.

Conley ME, Mathias D, Treadaway J, Minegishi Y, Rohrer J.

Am J Hum Genet. 1998 May;62(5):1034-43.

PubMed [citation]

PMID:: 9545398
PMCID:: PMC1377085

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001565324.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 622 of the BTK protein (p.Ala622Pro). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and proline. This variant has been observed in individual(s) with agammaglobulinemia (PMID: 8938104, 9545398). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BTK protein function.

#	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

ClinVar

Relating variation to medicine