17-73565238-A-G

Variant names:

• chr17-73565238-A-G
• rs9889955
• NM_001144952.2:c.65-57641T>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.65-57641T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,062 control chromosomes in the GnomAD database, including 3,193 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 0.20 (3193 hom., cov: 33)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK2	NM_001144952.2	c.65-57641T>C		intron_variant	Intron 1 of 44	ENST00000392650.8	NP_001138424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8	c.65-57641T>C		intron_variant	Intron 1 of 44	5	NM_001144952.2	ENSP00000376421.3

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30266 AN: 151942 Hom.: 3185 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.199 AC: 30300 AN: 152062 Hom.: 3193 Cov.: 33 AF XY: 0.198 AC XY: 14747 AN XY: 74328

African (AFR) AF: 0.265 AC: 10993 AN: 41444

American (AMR) AF: 0.148 AC: 2257 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3468

East Asian (EAS) AF: 0.169 AC: 875 AN: 5164

South Asian (SAS) AF: 0.202 AC: 974 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1922 AN: 10590

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12117 AN: 67976

Other (OTH) AF: 0.200 AC: 422 AN: 2110

Alfa AF: 0.184 Hom.: 10313

Bravo AF: 0.199

Asia WGS AF: 0.236 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.75
PhyloP100		0.029
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: rs9889955; hg19: chr17-71561377;