Genetic Variant CARD14:p.Asp15Gly (chr17-80181482-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366385.1(CARD14):c.44A>G(p.Asp15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D15D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Publications

0 publications found

Variant links:

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]

CARD14 Gene-Disease associations (from GenCC):

familial pityriasis rubra pilaris
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
psoriasis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P

CARD14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19636333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366385.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD14	NM_001366385.1	MANE Select	c.44A>G	p.Asp15Gly	missense	Exon 5 of 24	NP_001353314.1	Q9BXL6-1
CARD14	NM_024110.4		c.44A>G	p.Asp15Gly	missense	Exon 2 of 21	NP_077015.2	Q9BXL6-1
CARD14	NM_001257970.1		c.44A>G	p.Asp15Gly	missense	Exon 2 of 15	NP_001244899.1	Q9BXL6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD14	ENST00000648509.2	MANE Select	c.44A>G	p.Asp15Gly	missense	Exon 5 of 24	ENSP00000498071.1	Q9BXL6-1
CARD14	ENST00000344227.6	TSL:1	c.44A>G	p.Asp15Gly	missense	Exon 2 of 21	ENSP00000344549.2	Q9BXL6-1
CARD14	ENST00000570421.5	TSL:1	c.44A>G	p.Asp15Gly	missense	Exon 2 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000481

AC:

AN:

208060

AF XY:

0.00000891

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000323

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

0.0033

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.058

Eigen_PC

Benign

0.038

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.68

M_CAP

Benign

0.031

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

3.3

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.053

Sift

Benign

0.053

Sift4G

Benign

0.22

Polyphen

0.083

Vest4

0.15

MutPred

0.20

Loss of disorder (P = 0.1161)

MVP

0.86

MPC

0.25

ClinPred

0.39

GERP RS

4.3

Varity_R

0.32

gMVP

0.60

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over