rs281875212

Positions:

• chr17-80183987-G-A
• chr17-80183987-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM5 PP5

The NM_001366385.1(CARD14):​c.424G>A​(p.Glu142Lys) variant causes a missense 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E142G) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CARD14 NM_001366385.1 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 2.52

Genes affected

CARD14 (HGNC:16446): (caspase recruitment domain family member 14) This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. Members of this protein family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control. This protein has been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-80183988-A-G is described in Lovd as [Pathogenic].
• PP5: Variant 17-80183987-G-A is Pathogenic according to our data. Variant chr17-80183987-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 31610.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-80183987-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.424G>A	p.Glu142Lys	missense_variant	7/24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.424G>A	p.Glu142Lys	missense_variant	7/24		NM_001366385.1	ENSP00000498071	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Psoriasis 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 04, 2012

- -

not provided Other:1

not provided, no classification provided

literature only

UniProtKB/Swiss-Prot

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T;T;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	.;.;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.7	M;M;M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.25	.;.;.;N
REVEL	Benign	0.26
Sift	Benign	1.0	.;.;.;T
Sift4G	Uncertain	0.014	D;.;D;D
Polyphen		0.99	D;D;.;D
Vest4		0.32
MutPred		0.27		Gain of MoRF binding (P = 0.0169);Gain of MoRF binding (P = 0.0169);Gain of MoRF binding (P = 0.0169);Gain of MoRF binding (P = 0.0169);
MVP		0.92
MPC		0.69
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.19
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs281875212; hg19: chr17-78157786;