17-73540586-T-G

Variant names:

• chr17-73540586-T-G
• rs1872087
• NM_001144952.2:c.65-32989A>C

Variant summary

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

The NM_001144952.2(SDK2):​c.65-32989A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,868 control chromosomes in the GnomAD database, including 24,361 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 0.56 (24361 hom., cov: 33)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144952.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDK2	NM_001144952.2	MANE Select	c.65-32989A>C		intron	N/A	NP_001138424.1	Q58EX2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDK2	ENST00000392650.8	TSL:5 MANE Select	c.65-32989A>C		intron	N/A	ENSP00000376421.3	Q58EX2-1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85661 AN: 151748 Hom.: 24338 Cov.: 33

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.565 AC: 85736 AN: 151868 Hom.: 24361 Cov.: 33 AF XY: 0.567 AC XY: 42090 AN XY: 74204

African (AFR) AF: 0.551 AC: 22817 AN: 41404

American (AMR) AF: 0.477 AC: 7292 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3468

East Asian (EAS) AF: 0.640 AC: 3294 AN: 5150

South Asian (SAS) AF: 0.642 AC: 3084 AN: 4800

European-Finnish (FIN) AF: 0.641 AC: 6753 AN: 10542

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.569 AC: 38642 AN: 67898

Other (OTH) AF: 0.576 AC: 1218 AN: 2114

Alfa AF: 0.568 Hom.: 95013

Bravo AF: 0.550

Asia WGS AF: 0.636 AC: 2212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		0.31
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: rs1872087; hg19: chr17-71536725;