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NM_012452.3(TNFRSF13B):c.204dup (p.Leu69fs) AND Common Variable Immune Deficiency, Dominant

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 14, 2016
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:
RCV000380683.6

Allele description [Variation Report for NM_012452.3(TNFRSF13B):c.204dup (p.Leu69fs)]

NM_012452.3(TNFRSF13B):c.204dup (p.Leu69fs)

Gene:
TNFRSF13B:TNF receptor superfamily member 13B [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_012452.3(TNFRSF13B):c.204dup (p.Leu69fs)
HGVS:
  • NC_000017.11:g.16948979dup
  • NG_007281.1:g.28110dup
  • NM_012452.3:c.204dupMANE SELECT
  • NP_036584.1:p.Leu69fs
  • LRG_120:g.28110dup
  • NC_000017.10:g.16852292_16852293insT
  • NC_000017.10:g.16852293dup
  • NM_012452.2:c.204dupA
  • NM_012452.3:c.204dup
  • NM_012452.3:c.204dupAMANE SELECT
Protein change:
L69fs
Links:
OMIM: 604907.0004; dbSNP: rs72553875
NCBI 1000 Genomes Browser:
rs72553875
Molecular consequence:
  • NM_012452.3:c.204dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Common Variable Immune Deficiency, Dominant
Identifiers:
MedGen: CN239265

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000400921Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification 20161018)
Uncertain significance
(Jun 14, 2016)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

ICSL_Variant_Classification_20161018.pdf

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

TACI is mutant in common variable immunodeficiency and IgA deficiency.

Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS.

Nat Genet. 2005 Aug;37(8):829-34. Epub 2005 Jul 10.

PubMed [citation]
PMID:
16007086

TNFRSF13B/TACI alterations in Greek patients with antibody deficiencies.

Speletas M, Mamara A, Papadopoulou-Alataki E, Iordanakis G, Liadaki K, Bardaka F, Kanariou M, Germenis AE.

J Clin Immunol. 2011 Aug;31(4):550-9. doi: 10.1007/s10875-011-9536-4. Epub 2011 May 6.

PubMed [citation]
PMID:
21547394
See all PubMed Citations (6)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000400921.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The c.204dupA (p.Leu69ThrfsTer12) variant is a frameshift variant and is predicted to result in a premature termination of the protein. The p.Leu69ThrfsTer12 variant has been reported in at least five studies in individuals with either CVID or IgA deficiency (Castigli et al. 2005; Salzer et al. 2009; Speletas et al. 2011; Freiberger et al. 2012; Pulvirenti et al. 2016) and found in a compound heterozygous state with a missense variant in three patients with CVID and in a heterozygous state in six individuals with IgA deficiency. One multigenerational family study showed this variant segregating with disease in individuals with IgA deficiency or CVID, suggesting clinical heterogeneity with a potential spectrum of disease (Castigli et al. 2005). The p.Leu69ThrfsTer12 variant was absent from at least 1250 controls, but is reported at a frequency of 0.00109 in the European American population of the Exome Sequencing Project. Functional studies show that the p.Leu69ThrfsTer12 variant results in a severely impaired secretion of IgG and IgA in B cells in response to the TACI ligand, APRIL (Castigli et al. 2005). Castigli et al. (2005) also showed there was no detectable protein product on the surface of 293 cells carrying the p.Leu69ThrfsTer12 variant. However, Salzer et al. (2009) showed a single EBV-transformed cell line carrying a heterozygous p.Leu69ThrfsTer12 variant displayed no significant differences in TACI expression or ligand binding capacity compared with controls. Based on the potential impact of frameshift variants and the supporting evidence, the p.Leu69ThrfsTer12 variant is classified as a variant of unknown significance but suspicious for pathogenicity for common variable immune deficiency.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 7, 2024