17-80206788-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001366385.1(CARD14):c.2692-182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 412,262 control chromosomes in the GnomAD database, including 63,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18704 hom., cov: 32)
  • Exomes 𝑓: 0.58 (44593 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.236

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 17-80206788-A-G is Benign according to our data. Variant chr17-80206788-A-G is described in ClinVar as [Benign]. Clinvar id is 1255138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD14	NM_001366385.1	c.2692-182A>G		intron_variant		ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2	c.2692-182A>G		intron_variant			NM_001366385.1	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72742 AN: 151850 Hom.: 18713 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.581 AC: 151252 AN: 260294 Hom.: 44593 Cov.: 3 AF XY: 0.582 AC XY: 78261 AN XY: 134408

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.562

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.479 AC: 72742 AN: 151968 Hom.: 18704 Cov.: 32 AF XY: 0.479 AC XY: 35572 AN XY: 74264

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.480

Alfa AF: 0.421 Hom.: 1400

Bravo AF: 0.458

Asia WGS AF: 0.517 AC: 1796 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.33
Dann	Benign	0.10

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

Other links and lift over

dbSNP: rs4889837; hg19: chr17-78180587;