Genetic Variant NM_001366385.1:c.2692-182A>G (chr17-80206788-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.236

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.2692-182A>G		intron_variant	Intron 22 of 23	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2 link	c.2692-182A>G		intron_variant	Intron 22 of 23		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72742

AN:

151850

Hom.:

18713

Cov.:

show subpopulations

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.:

AF XY:

0.582

AC XY:

78261

AN XY:

134408

show subpopulations

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.:

AF XY:

0.479

AC XY:

35572

AN XY:

74264

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 05, 2019

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

- -

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

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