chr17-80205667-G-A

Variant names:

• chr17-80205667-G-A
• rs200394665
• NM_001366385.1:c.2691+15G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001366385.1(CARD14):​c.2691+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,537,404 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (7 hom.)
• Consequence: CARD14 NM_001366385.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.43
• Publications: 0 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]

ENSG00000262580 (HGNC:):

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 (BayesDel_noAF=-0.94).
• BP6: Variant 17-80205667-G-A is Benign according to our data. Variant chr17-80205667-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 402488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00122 (186/152254) while in subpopulation AMR AF = 0.00353 (54/15292). AF 95% confidence interval is 0.00278. There are 0 homozygotes in GnomAd4. There are 90 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 186 AD gene.

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.2691+15G>A		intron	N/A	NP_001353314.1
	CARD14	NM_024110.4		c.2691+15G>A		intron	N/A	NP_077015.2
	CARD14	NR_047566.2		n.2828+15G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.2691+15G>A		intron	N/A	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.2691+15G>A		intron	N/A	ENSP00000344549.2
	ENSG00000262580	ENST00000572730.1	TSL:3	n.283C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00221 AC: 323 AN: 146448 AF XY: 0.00249

Gnomad AFR exome AF: 0.000100

Gnomad AMR exome AF: 0.00395

Gnomad ASJ exome AF: 0.00879

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.00377

GnomAD4 exome AF: 0.00121 AC: 1676 AN: 1385150 Hom.: 7 Cov.: 36 AF XY: 0.00133 AC XY: 907 AN XY: 681716

African (AFR) AF: 0.000280 AC: 9 AN: 32134

American (AMR) AF: 0.00367 AC: 130 AN: 35460

Ashkenazi Jewish (ASJ) AF: 0.00644 AC: 148 AN: 22986

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37142

South Asian (SAS) AF: 0.00463 AC: 345 AN: 74472

European-Finnish (FIN) AF: 0.0000624 AC: 3 AN: 48062

Middle Eastern (MID) AF: 0.0113 AC: 49 AN: 4336

European-Non Finnish (NFE) AF: 0.000783 AC: 840 AN: 1073164

Other (OTH) AF: 0.00263 AC: 151 AN: 57394

GnomAD4 genome AF: 0.00122 AC: 186 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.00121 AC XY: 90 AN XY: 74442

African (AFR) AF: 0.000337 AC: 14 AN: 41550

American (AMR) AF: 0.00353 AC: 54 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000971 AC: 66 AN: 68002

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00274 Hom.: 1

Bravo AF: 0.00153

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Pityriasis rubra pilaris;C1864497:Psoriasis 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.58
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200394665; hg19: chr17-78179466;