17-73350681-C-G

Position:

• chr17-73350681-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001144952.2(SDK2):​c.5868G>C​(p.Gln1956His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SDK2 NM_001144952.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDK2	NM_001144952.2	c.5868G>C	p.Gln1956His	missense_variant	42/45	ENST00000392650.8
SDK2	XM_011524914.3	c.5811G>C	p.Gln1937His	missense_variant	41/44
SDK2	XM_011524915.3	c.5868G>C	p.Gln1956His	missense_variant	42/46
SDK2	XM_047436313.1	c.5811G>C	p.Gln1937His	missense_variant	41/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDK2	ENST00000392650.8	c.5868G>C	p.Gln1956His	missense_variant	42/45	5	NM_001144952.2	P1
SDK2	ENST00000424778.1	c.3339G>C	p.Gln1113His	missense_variant	24/27	5
SDK2	ENST00000410094.5	n.941G>C		non_coding_transcript_exon_variant	7/10	5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.5868G>C (p.Q1956H) alteration is located in exon 42 (coding exon 42) of the SDK2 gene. This alteration results from a G to C substitution at nucleotide position 5868, causing the glutamine (Q) at amino acid position 1956 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.21
Sift	Benign	0.065	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.55	P;.
Vest4		0.78
MutPred		0.63		Gain of sheet (P = 0.039);.;
MVP		0.73
MPC		0.86
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.43
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-71346820;