chr17-73338819-C-T

Variant names:

• chr17-73338819-C-T
• rs749515894
• NM_001144952.2:c.6287G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144952.2(SDK2):​c.6287G>A​(p.Arg2096Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: SDK2 NM_001144952.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31894016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK2	NM_001144952.2	c.6287G>A	p.Arg2096Lys	missense_variant	Exon 45 of 45	ENST00000392650.8	NP_001138424.1
SDK2	XM_011524914.3	c.6230G>A	p.Arg2077Lys	missense_variant	Exon 44 of 44		XP_011523216.1
SDK2	XM_011524915.3	c.6287G>A	p.Arg2096Lys	missense_variant	Exon 45 of 46		XP_011523217.1
SDK2	XM_047436313.1	c.6230G>A	p.Arg2077Lys	missense_variant	Exon 44 of 45		XP_047292269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8	c.6287G>A	p.Arg2096Lys	missense_variant	Exon 45 of 45	5	NM_001144952.2	ENSP00000376421.3
SDK2	ENST00000424778.1	c.3758G>A	p.Arg1253Lys	missense_variant	Exon 27 of 27	5		ENSP00000407098.1
SDK2	ENST00000410094.5	n.1360G>A		non_coding_transcript_exon_variant	Exon 10 of 10	5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.095
Sift	Benign	0.81	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.13	B;.
Vest4		0.33
MutPred		0.34		Gain of methylation at R2096 (P = 0.0019);.;
MVP		0.70
MPC		0.88
ClinPred		0.93	D
GERP RS		4.7
Varity_R		0.23
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749515894; hg19: chr17-71334958;