rs2289541

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366385.1(CARD14):c.2648G>A(p.Arg883His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,566,766 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 183 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.22

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 links:

ENSG00000262580 (HGNC:):

ENSG00000262580 links:

SGSH (HGNC:10818): (N-sulfoglucosamine sulfohydrolase) This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]

SGSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016128719).

BP6

Variant 17-80205609-G-A is Benign according to our data. Variant chr17-80205609-G-A is described in ClinVar as [Benign]. Clinvar id is 458097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80205609-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.08 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.2648G>A	p.Arg883His	missense_variant	Exon 22 of 24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2 link	c.2648G>A	p.Arg883His	missense_variant	Exon 22 of 24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.00371

AC:

564

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0864

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00751

AC:

1309

AN:

174330

Hom.:

AF XY:

0.00735

AC XY:

680

AN XY:

92570

show subpopulations

Gnomad AFR exome

AF:

0.00184

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.000468

Gnomad EAS exome

AF:

0.0869

Gnomad SAS exome

AF:

0.00280

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.000225

Gnomad OTH exome

AF:

0.00532

GnomAD4 exome

AF:

0.00305

AC:

4313

AN:

1414542

Hom.:

183

Cov.:

AF XY:

0.00304

AC XY:

2128

AN XY:

699172

show subpopulations

Gnomad4 AFR exome

AF:

0.000737

Gnomad4 AMR exome

AF:

0.000345

Gnomad4 ASJ exome

AF:

0.000636

Gnomad4 EAS exome

AF:

0.0919

Gnomad4 SAS exome

AF:

0.00307

Gnomad4 FIN exome

AF:

0.000100

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.00714

GnomAD4 genome

AF:

0.00371

AC:

564

AN:

152224

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0866

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00283

Hom.:

Bravo

AF:

0.00416

ESP6500AA

AF:

0.00274

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00545

AC:

647

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 32199921) -

Autoinflammatory syndrome

Benign:1

Mar 11, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.051

DANN

Benign

0.87

DEOGEN2

Benign

0.0022

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.53

.;.;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.27

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.80

.;.;N

REVEL

Benign

0.041

Sift

Benign

0.53

.;.;T

Sift4G

Benign

0.43

T;.;T

Polyphen

0.0

B;B;B

Vest4

0.034

MVP

0.31

MPC

0.18

ClinPred

0.0019

GERP RS

-8.8

Varity_R

0.027

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over