17-73350240-G-T

Position:

• chr17-73350240-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001144952.2(SDK2):​c.6035C>A​(p.Thr2012Asn) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SDK2 NM_001144952.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.66

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41166657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK2	NM_001144952.2	c.6035C>A	p.Thr2012Asn	missense_variant	43/45	ENST00000392650.8	NP_001138424.1
SDK2	XM_011524914.3	c.5978C>A	p.Thr1993Asn	missense_variant	42/44		XP_011523216.1
SDK2	XM_011524915.3	c.6035C>A	p.Thr2012Asn	missense_variant	43/46		XP_011523217.1
SDK2	XM_047436313.1	c.5978C>A	p.Thr1993Asn	missense_variant	42/45		XP_047292269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8	c.6035C>A	p.Thr2012Asn	missense_variant	43/45	5	NM_001144952.2	ENSP00000376421	P1
SDK2	ENST00000424778.1	c.3506C>A	p.Thr1169Asn	missense_variant	25/27	5		ENSP00000407098
SDK2	ENST00000410094.5	n.1108C>A		non_coding_transcript_exon_variant	8/10	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 857088 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 422618

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

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

Dec 12, 2023

The c.6035C>A (p.T2012N) alteration is located in exon 43 (coding exon 43) of the SDK2 gene. This alteration results from a C to A substitution at nucleotide position 6035, causing the threonine (T) at amino acid position 2012 to be replaced by an asparagine (N). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.41	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.16
Sift	Benign	0.18	T;T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.94	P;.
Vest4		0.75
MutPred		0.36		Loss of phosphorylation at T2012 (P = 0.017);.;
MVP		0.86
MPC		0.95
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-71346379;