rs11869008

Variant names:

• chr17-73424732-A-C
• rs11869008
• NM_001144952.2:c.1584-640T>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.1584-640T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,170 control chromosomes in the GnomAD database, including 44,149 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 0.75 (44149 hom., cov: 33)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK2	NM_001144952.2	c.1584-640T>G		intron_variant	Intron 12 of 44	ENST00000392650.8	NP_001138424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8	c.1584-640T>G		intron_variant	Intron 12 of 44	5	NM_001144952.2	ENSP00000376421.3
SDK2	ENST00000479356.1	n.615-640T>G		intron_variant	Intron 5 of 32	1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114693 AN: 152052 Hom.: 44120 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.754 AC: 114772 AN: 152170 Hom.: 44149 Cov.: 33 AF XY: 0.746 AC XY: 55452 AN XY: 74376

African (AFR) AF: 0.757 AC: 31440 AN: 41512

American (AMR) AF: 0.819 AC: 12528 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2433 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1408 AN: 5162

South Asian (SAS) AF: 0.610 AC: 2945 AN: 4824

European-Finnish (FIN) AF: 0.702 AC: 7424 AN: 10580

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54047 AN: 68008

Other (OTH) AF: 0.769 AC: 1624 AN: 2112

Alfa AF: 0.788 Hom.: 55289

Bravo AF: 0.763

Asia WGS AF: 0.478 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.66
PhyloP100		-0.11
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: rs11869008; hg19: chr17-71420871;