rs1021652

Variant names:

• chr17-73407751-A-G
• rs1021652
• NM_001144952.2:c.2485-5610T>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.2485-5610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 152,276 control chromosomes in the GnomAD database, including 69,016 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 0.95 (69016 hom., cov: 32)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.983 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.2485-5610T>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.2485-5610T>C		intron	N/A	ENSP00000376421.3	Q58EX2-1
	SDK2	ENST00000479356.1	TSL:1	n.1516-5610T>C		intron	N/A
	SDK2	ENST00000424778.1	TSL:5	c.13-5610T>C		intron	N/A	ENSP00000407098.1	H7C2P2

Frequencies

GnomAD3 genomes AF: 0.951 AC: 144718 AN: 152158 Hom.: 68970 Cov.: 32

Gnomad AFR AF: 0.921

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.951 AC: 144822 AN: 152276 Hom.: 69016 Cov.: 32 AF XY: 0.945 AC XY: 70362 AN XY: 74452

African (AFR) AF: 0.921 AC: 38246 AN: 41542

American (AMR) AF: 0.920 AC: 14066 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3335 AN: 3472

East Asian (EAS) AF: 0.850 AC: 4394 AN: 5172

South Asian (SAS) AF: 0.909 AC: 4388 AN: 4828

European-Finnish (FIN) AF: 0.926 AC: 9830 AN: 10610

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.990 AC: 67337 AN: 68038

Other (OTH) AF: 0.961 AC: 2034 AN: 2116

Alfa AF: 0.971 Hom.: 10100

Bravo AF: 0.948

Asia WGS AF: 0.878 AC: 3056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.36
PhyloP100		0.42
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1021652;

hg19: chr17-71403890;