rs3816995

Variant names:

• chr17-73339121-G-A
• rs3816995
• NM_001144952.2:c.6166-181C>T

Variant summary

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

The NM_001144952.2(SDK2):​c.6166-181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,004 control chromosomes in the GnomAD database, including 12,782 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 0.40 (12782 hom., cov: 32)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.487 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.6166-181C>T		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.6166-181C>T		intron	N/A	ENSP00000376421.3	Q58EX2-1
	SDK2	ENST00000424778.1	TSL:5	c.3637-181C>T		intron	N/A	ENSP00000407098.1	H7C2P2
	SDK2	ENST00000410094.5	TSL:5	n.1239-181C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60667 AN: 151884 Hom.: 12762 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.400 AC: 60735 AN: 152004 Hom.: 12782 Cov.: 32 AF XY: 0.398 AC XY: 29600 AN XY: 74290

African (AFR) AF: 0.297 AC: 12327 AN: 41492

American (AMR) AF: 0.497 AC: 7592 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3468

East Asian (EAS) AF: 0.157 AC: 815 AN: 5178

South Asian (SAS) AF: 0.327 AC: 1575 AN: 4816

European-Finnish (FIN) AF: 0.409 AC: 4315 AN: 10542

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31175 AN: 67916

Other (OTH) AF: 0.417 AC: 879 AN: 2108

Alfa AF: 0.437 Hom.: 50396

Bravo AF: 0.402

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.53
PhyloP100		-0.85
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: rs3816995; hg19: chr17-71335260;