rs12453316

Variant names:

• chr17-73519920-C-T
• rs12453316
• NM_001144952.2:c.65-12323G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001144952.2(SDK2):​c.65-12323G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,214 control chromosomes in the GnomAD database, including 6,561 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 0.26 (6561 hom., cov: 33)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: SDK2 NM_001144952.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.28
• Publications: 2 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

ENSG00000264985 (HGNC:58559):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 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.65-12323G>A		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.65-12323G>A		intron	N/A	ENSP00000376421.3	Q58EX2-1
	ENSG00000264985	ENST00000583712.2	TSL:5	n.2828C>T		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000264985	ENST00000655723.1		n.1137C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40242 AN: 152084 Hom.: 6560 Cov.: 33

Gnomad AFR AF: 0.0699

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.264 AC: 40248 AN: 152206 Hom.: 6561 Cov.: 33 AF XY: 0.266 AC XY: 19766 AN XY: 74410

African (AFR) AF: 0.0698 AC: 2898 AN: 41546

American (AMR) AF: 0.266 AC: 4066 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1036 AN: 5176

South Asian (SAS) AF: 0.381 AC: 1840 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3780 AN: 10596

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24615 AN: 67984

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.331 Hom.: 8069

Bravo AF: 0.246

Asia WGS AF: 0.274 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Benign	0.91
PhyloP100		3.3
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: rs12453316; hg19: chr17-71516059;