chr7-2944307-C-CCTTGACCAGCTCGTCATTGTAGCTGTCCCGCTCTTCCTTCAT

Position:

• chr7-2944307-C-CCTTGACCAGCTCGTCATTGTAGCTGTCCCGCTCTTCCTTCAT

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_032415.7(CARD11):​c.588_589insATGAAGGAAGAGCGGGACAGCTACAATGACGAGCTGGTCAAG​(p.Met183_Lys196dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CARD11 NM_032415.7 inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.148

Genes affected

CARD11 (HGNC:16393): (caspase recruitment domain family member 11) The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein has a domain structure similar to that of CARD14 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activated NF-kappaB and induced the phosphorylation of BCL10. [provided by RefSeq, Jul 2008]

CARD11-AS1 (HGNC:40766): (CARD11 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_032415.7.
• PP5: Variant 7-2944307-C-CCTTGACCAGCTCGTCATTGTAGCTGTCCCGCTCTTCCTTCAT is Pathogenic according to our data. Variant chr7-2944307-C-CCTTGACCAGCTCGTCATTGTAGCTGTCCCGCTCTTCCTTCAT is described in ClinVar as [Pathogenic]. Clinvar id is 1707407.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD11	NM_032415.7	c.588_589insATGAAGGAAGAGCGGGACAGCTACAATGACGAGCTGGTCAAG	p.Met183_Lys196dup	inframe_insertion	5/25	ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3	c.588_589insATGAAGGAAGAGCGGGACAGCTACAATGACGAGCTGGTCAAG	p.Met183_Lys196dup	inframe_insertion	6/26		NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD11	ENST00000396946.9	c.588_589insATGAAGGAAGAGCGGGACAGCTACAATGACGAGCTGGTCAAG	p.Met183_Lys196dup	inframe_insertion	5/25	1	NM_032415.7	ENSP00000380150	P1
CARD11-AS1	ENST00000423194.1	n.278_319dup		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 11b with atopic dermatitis Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

Molecular Diagnosis for Inborn Errors of Immunity, Hospital de Pediatria Garrahan

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-2983941;