NM_012452.3(TNFRSF13B):c.266G>A (p.Cys89Tyr) AND Immunodeficiency, common variable, 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 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:: RCV003101483.3

Allele description [Variation Report for NM_012452.3(TNFRSF13B):c.266G>A (p.Cys89Tyr)]

NM_012452.3(TNFRSF13B):c.266G>A (p.Cys89Tyr)

Gene:

TNFRSF13B:TNF receptor superfamily member 13B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_012452.3(TNFRSF13B):c.266G>A (p.Cys89Tyr)

HGVS:

NC_000017.11:g.16948917C>T
NG_007281.1:g.28172G>A
NM_012452.3:c.266G>AMANE SELECT
NP_036584.1:p.Cys89Tyr
LRG_120:g.28172G>A
NC_000017.10:g.16852231C>T

Protein change:

C89Y

Links:

dbSNP: rs746779126

NCBI 1000 Genomes Browser:

rs746779126

Molecular consequence:

NM_012452.3:c.266G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Immunodeficiency, common variable, 2
Synonyms:: ANTIBODY DEFICIENCY DUE TO TACI DEFECT; HYPOGAMMAGLOBULINEMIA DUE TO TACI DEFICIENCY; Hypogamma-globulinemia, acquired; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009413; MedGen: C3150354; Orphanet: 1572; OMIM: 240500

Recent activity

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Homo sapiens dual specificity phosphatase 3 (DUSP3), mRNA
Homo sapiens dual specificity phosphatase 3 (DUSP3), mRNA
gi|1519243468|ref|NM_004090.4|

Nucleotide
Homo sapiens potassium channel, subfamily K, member 9, mRNA (cDNA clone MGC:1382...
Homo sapiens potassium channel, subfamily K, member 9, mRNA (cDNA clone MGC:138270 IMAGE:8327533), complete cds
gi|85567009|gb|BC112065.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003441751	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19779048, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003441751

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2022)

germline

clinical testing

PubMed (2)
[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

Role of TNFRSF13B variants in patients with common variable immunodeficiency.

Martínez-Pomar N, Detková D, Arostegui JI, Alvarez A, Soler-Palacín P, Vidaller A, Espanol T, Sampalo A, de Gracia J, Hernandez M, Yagüe J, Matamoros N.

Blood. 2009 Sep 24;114(13):2846-8. doi: 10.1182/blood-2009-05-213025. No abstract available.

PubMed [citation]

PMID:: 19779048

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003441751.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 89 of the TNFRSF13B protein (p.Cys89Tyr). This variant is present in population databases (rs746779126, gnomAD 0.002%). This missense change has been observed in individual(s) with common variable immunodeficiency (PMID: 19779048). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.

#	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: Oct 20, 2024

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