Variant chr17-73348683-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144952.2(SDK2):c.6081T>G(p.Asp2027Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SDK2
NM_001144952.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.246

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23643598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SDK2	NM_001144952.2 linkuse as main transcript	c.6081T>G	p.Asp2027Glu	missense_variant	44/45	ENST00000392650.8	NP_001138424.1
SDK2	XM_011524914.3 linkuse as main transcript	c.6024T>G	p.Asp2008Glu	missense_variant	43/44		XP_011523216.1
SDK2	XM_011524915.3 linkuse as main transcript	c.6081T>G	p.Asp2027Glu	missense_variant	44/46		XP_011523217.1
SDK2	XM_047436313.1 linkuse as main transcript	c.6024T>G	p.Asp2008Glu	missense_variant	43/45		XP_047292269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8 linkuse as main transcript	c.6081T>G	p.Asp2027Glu	missense_variant	44/45	5	NM_001144952.2	ENSP00000376421	P1	Q58EX2-1
SDK2	ENST00000424778.1 linkuse as main transcript	c.3552T>G	p.Asp1184Glu	missense_variant	26/27	5		ENSP00000407098
SDK2	ENST00000410094.5 linkuse as main transcript	n.1154T>G		non_coding_transcript_exon_variant	9/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

249476

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

134920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459500

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2021

The c.6081T>G (p.D2027E) alteration is located in exon 44 (coding exon 44) of the SDK2 gene. This alteration results from a T to G substitution at nucleotide position 6081, causing the aspartic acid (D) at amino acid position 2027 to be replaced by a glutamic acid (E). 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

0.67

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.91

D;D

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.43

B;.

Vest4

0.79

MutPred

0.15

Gain of methylation at K2032 (P = 0.1188);.;

MVP

0.45

MPC

0.45

ClinPred

0.63

GERP RS

-2.1

Varity_R

0.72

gMVP

0.39

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

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