chr17-80208215-G-A

Variant names:

• chr17-80208215-G-A
• rs34850974
• NM_001366385.1:c.2885G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.740
• Publications: 5 publications found

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]

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

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	NM_001366385.1	MANE Select	c.2885G>A	p.Arg962Gln	missense	Exon 24 of 24	NP_001353314.1
	CARD14	NM_024110.4		c.2885G>A	p.Arg962Gln	missense	Exon 21 of 21	NP_077015.2
	CARD14	NR_047566.2		n.3022G>A		non_coding_transcript_exon	Exon 22 of 22

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.2885G>A	p.Arg962Gln	missense	Exon 24 of 24	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.2885G>A	p.Arg962Gln	missense	Exon 21 of 21	ENSP00000344549.2
	CARD14	ENST00000651672.1		c.2912G>A	p.Arg971Gln	missense	Exon 23 of 23	ENSP00000499145.1

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6432 AN: 152160 Hom.: 489 Cov.: 33

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

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.: 32 AF XY: 0.00368 AC XY: 2560 AN XY: 694964

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: 0 AN: 25216

East Asian (EAS) AF: 0.0000268 AC: 1 AN: 37344

South Asian (SAS) AF: 0.000300 AC: 24 AN: 80010

European-Finnish (FIN) AF: 0.0000205 AC: 1 AN: 48666

Middle Eastern (MID) AF: 0.00685 AC: 37 AN: 5398

European-Non Finnish (NFE) AF: 0.000220 AC: 238 AN: 1083802

Other (OTH) AF: 0.00944 AC: 551 AN: 58372

GnomAD4 genome AF: 0.0423 AC: 6446 AN: 152278 Hom.: 491 Cov.: 33 AF XY: 0.0414 AC XY: 3080 AN XY: 74462

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: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68014

Other (OTH) AF: 0.0279 AC: 59 AN: 2116

Alfa AF: 0.0123 Hom.: 90

Bravo AF: 0.0474

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.139 AC: 603

ESP6500EA AF: 0.00106 AC: 9

ExAC AF: 0.0103 AC: 1192

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.47
DANN	Benign	0.81
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.74
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.028
Sift	Benign	0.24	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.067
MPC		0.17
ClinPred		0.0022	T
GERP RS		-7.3
Varity_R		0.022
gMVP		0.20
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34850974; hg19: chr17-78182014;