Genetic Variant CARD14:p.Asn237Asp (chr17-80188410-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366385.1(CARD14):c.709A>G(p.Asn237Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N237H) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.102

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04570526).

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.709A>G	p.Asn237Asp	missense	Exon 8 of 24	NP_001353314.1	Q9BXL6-1
CARD14	NM_024110.4		c.709A>G	p.Asn237Asp	missense	Exon 5 of 21	NP_077015.2	Q9BXL6-1
CARD14	NM_001257970.1		c.709A>G	p.Asn237Asp	missense	Exon 5 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.709A>G	p.Asn237Asp	missense	Exon 8 of 24	ENSP00000498071.1	Q9BXL6-1
CARD14	ENST00000344227.6	TSL:1	c.709A>G	p.Asn237Asp	missense	Exon 5 of 21	ENSP00000344549.2	Q9BXL6-1
CARD14	ENST00000570421.5	TSL:1	c.709A>G	p.Asn237Asp	missense	Exon 5 of 15	ENSP00000461806.1	Q9BXL6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458684

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725568

African (AFR)

AF:

0.00

AC:

AN:

33370

American (AMR)

AF:

0.00

AC:

AN:

44272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39352

South Asian (SAS)

AF:

0.00

AC:

AN:

85540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110672

Other (OTH)

AF:

0.00

AC:

AN:

60274

GnomAD4 genome

Cov.:

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

0.065

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0051

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.50

M_CAP

Benign

0.0039

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.69

PhyloP100

-0.10

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.40

REVEL

Benign

0.017

Sift

Benign

0.51

Sift4G

Benign

0.091

Polyphen

0.0

Vest4

0.095

MutPred

0.14

Loss of stability (P = 0.0729)

MVP

0.41

MPC

0.17

ClinPred

0.053

GERP RS

0.53

Varity_R

0.048

gMVP

0.038

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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