rs34850974

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366385.1(CARD14):c.2885G>A(p.Arg962Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 1,559,890 control chromosomes in the GnomAD database, including 884 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R962W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.042 ( 491 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 393 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.740

Publications

5 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 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 Gene-Disease associations (from GenCC):

mucopolysaccharidosis type 3A
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Orphanet, Myriad Women’s Health, G2P

SGSH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011251271).

BP6

Variant 17-80208215-G-A is Benign according to our data. Variant chr17-80208215-G-A is described in ClinVar as Benign. ClinVar VariationId is 458102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.2885G>A	p.Arg962Gln	missense_variant	Exon 24 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.2885G>A	p.Arg962Gln	missense_variant	Exon 24 of 24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.0423

AC:

6432

AN:

152160

Hom.:

489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0282

GnomAD2 exomes

AF:

0.0103

AC:

1738

AN:

168668

AF XY:

0.00783

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.00684

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.00439

GnomAD4 exome

AF:

0.00431

AC:

6061

AN:

1407612

Hom.:

393

Cov.:

AF XY:

0.00368

AC XY:

2560

AN XY:

694964

show subpopulations

African (AFR)

AF:

0.151

AC:

4923

AN:

32582

American (AMR)

AF:

0.00790

AC:

286

AN:

36222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25216

East Asian (EAS)

AF:

0.0000268

AC:

AN:

37344

South Asian (SAS)

AF:

0.000300

AC:

AN:

80010

European-Finnish (FIN)

AF:

0.0000205

AC:

AN:

48666

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

5398

European-Non Finnish (NFE)

AF:

0.000220

AC:

238

AN:

1083802

Other (OTH)

AF:

0.00944

AC:

551

AN:

58372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

259

518

776

1035

1294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0423

AC:

6446

AN:

152278

Hom.:

491

Cov.:

AF XY:

0.0414

AC XY:

3080

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.147

AC:

6113

AN:

41542

American (AMR)

AF:

0.0157

AC:

241

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00145

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68014

Other (OTH)

AF:

0.0279

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

285

570

855

1140

1425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.0474

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.139

AC:

603

ESP6500EA

AF:

0.00106

AC:

ExAC

AF:

0.0103

AC:

1192

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammatory syndrome

Benign:1

Feb 04, 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

0.085

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.47

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.65

.;.;T

MetaRNN

Benign

0.0011

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

PhyloP100

-0.74

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.36

.;.;N

REVEL

Benign

0.028

Sift

Benign

0.24

.;.;T

Sift4G

Benign

0.15

T;.;T

Polyphen

0.0

B;B;B

Vest4

0.067

MPC

0.17

ClinPred

0.0022

GERP RS

-7.3

Varity_R

0.022

gMVP

0.20

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over