NM_000061.3(BTK):c.1690T>C (p.Ser564Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 30, 2021
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:: RCV002208767.2

Allele description [Variation Report for NM_000061.3(BTK):c.1690T>C (p.Ser564Pro)]

NM_000061.3(BTK):c.1690T>C (p.Ser564Pro)

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.1690T>C (p.Ser564Pro)

HGVS:

NC_000023.11:g.101353930A>G
NG_009616.1:g.37295T>C
NG_011734.1:g.40T>C
NM_000061.3:c.1690T>CMANE SELECT
NM_001287344.2:c.1792T>C
NM_001287345.2:c.1162T>C
NP_000052.1:p.Ser564Pro
NP_001274273.1:p.Ser598Pro
NP_001274274.1:p.Ser388Pro
LRG_128:g.37295T>C
NC_000023.10:g.100608918A>G

Protein change:

S388P

Links:

dbSNP: rs2147424985

NCBI 1000 Genomes Browser:

rs2147424985

Molecular consequence:

NM_000061.3:c.1690T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287344.2:c.1792T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287345.2:c.1162T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: X-linked agammaglobulinemia (XLA)
Synonyms:: IMMUNODEFICIENCY 1; Bruton's agammaglobulinemia; AGAMMAGLOBULINEMIA, X-LINKED, TYPE 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010421; MedGen: C0221026; Orphanet: 229717; Orphanet: 47; OMIM: 300755

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

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
SCV002495913	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002495913

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 30, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV002495913.2

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

Description

BTK NM_000061.2 exon 17 p.Ser564Pro (c.1690T>C): This variant has been reported in the literature as associated with X-linked Agammaglobulinaemia in at least one patient (publication unavailable for review: Wang (2012) Chin J Evid Based Pediatr Vol. 7 (1): 4-10), and is not present in large control databases. Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. This missense variant is present in the kinase (SH1) domain of the BTK protein (PMID: 15024743). Down regulation of BTK function is associated with X-linked agammaglobulinemia (XLA). In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#	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: Dec 24, 2023

ClinVar

Relating variation to medicine