chr17-73492000-A-G

Variant names:

• chr17-73492000-A-G
• rs1872076
• NM_001144952.2:c.224+15438T>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.224+15438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,982 control chromosomes in the GnomAD database, including 13,657 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 0.42 (13657 hom., cov: 32)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK2	NM_001144952.2	c.224+15438T>C		intron_variant	Intron 2 of 44	ENST00000392650.8	NP_001138424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8	c.224+15438T>C		intron_variant	Intron 2 of 44	5	NM_001144952.2	ENSP00000376421.3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63737 AN: 151864 Hom.: 13649 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.420 AC: 63789 AN: 151982 Hom.: 13657 Cov.: 32 AF XY: 0.423 AC XY: 31396 AN XY: 74296

African (AFR) AF: 0.472 AC: 19547 AN: 41430

American (AMR) AF: 0.496 AC: 7579 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2747 AN: 5148

South Asian (SAS) AF: 0.401 AC: 1935 AN: 4824

European-Finnish (FIN) AF: 0.382 AC: 4043 AN: 10570

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25244 AN: 67946

Other (OTH) AF: 0.388 AC: 818 AN: 2106

Alfa AF: 0.385 Hom.: 33870

Bravo AF: 0.436

Asia WGS AF: 0.470 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.39
PhyloP100		0.18
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: rs1872076; hg19: chr17-71488139;