7-2923155-G-C

Position:

• chr7-2923155-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_032415.7(CARD11):​c.2119C>G​(p.Arg707Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CARD11 NM_032415.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CARD11. . Gene score misZ 3.5439 (greater than the threshold 3.09). Trascript score misZ 3.7177 (greater than threshold 3.09). GenCC has associacion of gene with BENTA disease, immunodeficiency 11b with atopic dermatitis, severe combined immunodeficiency due to CARD11 deficiency.
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD11	NM_032415.7	c.2119C>G	p.Arg707Gly	missense_variant	16/25	ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3	c.2119C>G	p.Arg707Gly	missense_variant	17/26		NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD11	ENST00000396946.9	c.2119C>G	p.Arg707Gly	missense_variant	16/25	1	NM_032415.7	ENSP00000380150	P1
CARD11	ENST00000355508.3	c.532C>G	p.Arg178Gly	missense_variant	5/7	3		ENSP00000347695
CARD11	ENST00000698637.1	n.2445C>G		non_coding_transcript_exon_variant	16/24

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	31
DANN	Benign	0.95
DEOGEN2	Uncertain	0.79	D;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.54	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;D
Sift4G	Benign	0.090	T;.
Polyphen		0.012	B;.
Vest4		0.37
MutPred		0.48		Loss of sheet (P = 0.0037);.;
MVP		0.55
MPC		0.75
ClinPred		0.92	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.93		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.93		Position offset: 0
DS_DL_spliceai		0.23		Position offset: -23

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: chr7-2962789;