rs2289541

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.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. 15/21 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

Publications

10 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:

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 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=0.0016128719).

BP6

Variant 17-80205609-G-A is Benign according to our data. Variant chr17-80205609-G-A is described in ClinVar as Benign. ClinVar VariationId is 458097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

GnomAD2 exomes

AF:

0.00751

AC:

1309

AN:

174330

AF XY:

0.00735

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 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

African (AFR)

AF:

0.000737

AC:

AN:

32548

American (AMR)

AF:

0.000345

AC:

AN:

37674

Ashkenazi Jewish (ASJ)

AF:

0.000636

AC:

AN:

25176

East Asian (EAS)

AF:

0.0919

AC:

3440

AN:

37416

South Asian (SAS)

AF:

0.00307

AC:

247

AN:

80470

European-Finnish (FIN)

AF:

0.000100

AC:

AN:

50010

Middle Eastern (MID)

AF:

0.00143

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.000131

AC:

142

AN:

1087144

Other (OTH)

AF:

0.00714

AC:

418

AN:

58514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

194

389

583

778

972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.00371

AC:

564

AN:

152224

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41548

American (AMR)

AF:

0.000458

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.0866

AC:

447

AN:

5160

South Asian (SAS)

AF:

0.00559

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68004

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00221

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

(source)

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

PhyloP100

-1.2

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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