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NM_032415.7(CARD11):c.224G>A (p.Arg75Gln) AND none provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 1, 2019
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:
RCV001001176.3

Allele description

NM_032415.7(CARD11):c.224G>A (p.Arg75Gln)

Genes:
CARD11-AS1:CARD11 antisense RNA 1 [Gene - HGNC]
CARD11:caspase recruitment domain family member 11 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.2
Genomic location:
Preferred name:
NM_032415.7(CARD11):c.224G>A (p.Arg75Gln)
HGVS:
  • NC_000007.14:g.2945953C>T
  • NG_027759.1:g.102923G>A
  • NM_001324281.3:c.224G>A
  • NM_032415.7:c.224G>AMANE SELECT
  • NP_001311210.1:p.Arg75Gln
  • NP_115791.3:p.Arg75Gln
  • LRG_729t1:c.224G>A
  • LRG_729t2:c.224G>A
  • LRG_729:g.102923G>A
  • LRG_729p1:p.Arg75Gln
  • LRG_729p2:p.Arg75Gln
  • NC_000007.13:g.2985587C>T
  • NM_032415.5:c.224G>A
Protein change:
R75Q
Links:
dbSNP: rs1064795280
NCBI 1000 Genomes Browser:
rs1064795280
Molecular consequence:
  • NM_001324281.3:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032415.7:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001158328ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Likely pathogenic
(Aug 1, 2019) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158328.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The CARD11 c.224G>A; p.Arg75Gln variant (rs1064795280) is reported in the literature in an individual with symptoms of immunodeficiency (Dorjbal 2019). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism, but it is reported in ClinVar (Variation ID: 421663). The arginine at codon 75 is highly conserved, it occurs in the functionally important CARD domain, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Consistent with these predictions, cultured cells expressing the p.Arg75Gln exhibit defects in NF-KB and mTORC signaling, and co-transfection of p.Arg75Gln with wildtype CARD11 suggests the variant protein exerts a dominant negative effect on cellular NF-KB signaling (Dorjbal 2019). Based on available information, this variant is considered to be likely pathogenic. References: Dorjbal B et al. Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease. J Allergy Clin Immunol. 2019 Apr;143(4):1482-1495.

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

Last Updated: Dec 12, 2021