chr17-73554726-T-C

Variant names:

• chr17-73554726-T-C
• rs9913193
• NM_001144952.2:c.65-47129A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144952.2(SDK2):​c.65-47129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,162 control chromosomes in the GnomAD database, including 5,665 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5665 hom., cov: 33)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931
• Publications: 5 publications found

Genes affected

SDK2 (HGNC:19308): (sidekick cell adhesion molecule 2) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains two immunoglobulin domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. This protein, and a homologous mouse sequence, are very similar to the Drosophila sidekick gene product but the specific function of this superfamily member is not yet known. Evidence for alternative splicing at this gene locus has been observed but the full-length nature of additional variants has not yet been determined. [provided by RefSeq, Jul 2008]

SDK2 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK2	NM_001144952.2	c.65-47129A>G		intron_variant	Intron 1 of 44	ENST00000392650.8	NP_001138424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8	c.65-47129A>G		intron_variant	Intron 1 of 44	5	NM_001144952.2	ENSP00000376421.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40934 AN: 152042 Hom.: 5657 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40977 AN: 152162 Hom.: 5665 Cov.: 33 AF XY: 0.274 AC XY: 20345 AN XY: 74376

African (AFR) AF: 0.258 AC: 10717 AN: 41508

American (AMR) AF: 0.217 AC: 3313 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 886 AN: 3460

East Asian (EAS) AF: 0.479 AC: 2475 AN: 5172

South Asian (SAS) AF: 0.329 AC: 1588 AN: 4828

European-Finnish (FIN) AF: 0.343 AC: 3625 AN: 10582

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17424 AN: 67990

Other (OTH) AF: 0.272 AC: 576 AN: 2114

Alfa AF: 0.261 Hom.: 20868

Bravo AF: 0.259

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.70
DANN	Benign	0.61
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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: rs9913193; hg19: chr17-71550865;