17-73348661-C-T

Variant names:

Variant summary

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

The NM_001144952.2(SDK2):c.6103G>A(p.Asp2035Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,612,538 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SDK2
NM_001144952.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SDK2	NM_001144952.2 link	c.6103G>A	p.Asp2035Asn	missense_variant	Exon 44 of 45	ENST00000392650.8	NP_001138424.1	Q58EX2-1
SDK2	XM_011524914.3 link	c.6046G>A	p.Asp2016Asn	missense_variant	Exon 43 of 44		XP_011523216.1	Q58EX2-3
SDK2	XM_011524915.3 link	c.6103G>A	p.Asp2035Asn	missense_variant	Exon 44 of 46		XP_011523217.1
SDK2	XM_047436313.1 link	c.6046G>A	p.Asp2016Asn	missense_variant	Exon 43 of 45		XP_047292269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDK2	ENST00000392650.8 link	c.6103G>A	p.Asp2035Asn	missense_variant	Exon 44 of 45	5	NM_001144952.2	ENSP00000376421.3	Q58EX2-1
SDK2	ENST00000424778.1 link	c.3574G>A	p.Asp1192Asn	missense_variant	Exon 26 of 27	5		ENSP00000407098.1	H7C2P2
SDK2	ENST00000410094.5 link	n.1176G>A		non_coding_transcript_exon_variant	Exon 9 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460366

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726470

show subpopulations

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.6103G>A (p.D2035N) alteration is located in exon 44 (coding exon 44) of the SDK2 gene. This alteration results from a G to A substitution at nucleotide position 6103, causing the aspartic acid (D) at amino acid position 2035 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

0.48

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.19

Sift

Benign

0.052

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.99

D;.

Vest4

0.77

MutPred

0.19

Gain of methylation at K2032 (P = 0.0706);.;

MVP

0.73

MPC

0.67

ClinPred

0.97

GERP RS

4.8

Varity_R

0.36

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over