chr17-80205045-G-A

Variant names:

• chr17-80205045-G-A
• rs115102551
• NM_001366385.1:c.2409G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001366385.1(CARD14):​c.2409G>A​(p.Thr803Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,597,356 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T803T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0063 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00071 (11 hom.)
• Consequence: CARD14 NM_001366385.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0690
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-80205045-G-A is Benign according to our data. Variant chr17-80205045-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 527873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.069 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0063 (960/152306) while in subpopulation AFR AF = 0.0221 (917/41568). AF 95% confidence interval is 0.0209. There are 11 homozygotes in GnomAd4. There are 444 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 960 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.2409G>A	p.Thr803Thr	synonymous	Exon 21 of 24	NP_001353314.1
	CARD14	NM_024110.4		c.2409G>A	p.Thr803Thr	synonymous	Exon 18 of 21	NP_077015.2
	CARD14	NR_047566.2		n.2546G>A		non_coding_transcript_exon	Exon 19 of 22

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD14	ENST00000648509.2	MANE Select	c.2409G>A	p.Thr803Thr	synonymous	Exon 21 of 24	ENSP00000498071.1
	CARD14	ENST00000344227.6	TSL:1	c.2409G>A	p.Thr803Thr	synonymous	Exon 18 of 21	ENSP00000344549.2
	CARD14	ENST00000651672.1		c.2436G>A	p.Thr812Thr	synonymous	Exon 20 of 23	ENSP00000499145.1

Frequencies

GnomAD3 genomes AF: 0.00631 AC: 960 AN: 152188 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00166 AC: 387 AN: 233540 AF XY: 0.00121

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.000428

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000225

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.000715 AC: 1033 AN: 1445050 Hom.: 11 Cov.: 42 AF XY: 0.000626 AC XY: 449 AN XY: 716992

African (AFR) AF: 0.0261 AC: 865 AN: 33098

American (AMR) AF: 0.000533 AC: 23 AN: 43152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25422

East Asian (EAS) AF: 0.000229 AC: 9 AN: 39280

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52226

Middle Eastern (MID) AF: 0.000205 AC: 1 AN: 4884

European-Non Finnish (NFE) AF: 0.0000725 AC: 80 AN: 1102988

Other (OTH) AF: 0.000892 AC: 53 AN: 59416

GnomAD4 genome AF: 0.00630 AC: 960 AN: 152306 Hom.: 11 Cov.: 33 AF XY: 0.00596 AC XY: 444 AN XY: 74466

African (AFR) AF: 0.0221 AC: 917 AN: 41568

American (AMR) AF: 0.00176 AC: 27 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68012

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00225 Hom.: 3

Bravo AF: 0.00722

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Autoinflammatory syndrome Benign:1

Dec 20, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.6
DANN	Benign	0.79
PhyloP100		0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs115102551; hg19: chr17-78178844;