17-73338651-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001144952.2(SDK2):c.6455G>A(p.Arg2152His) variant causes a missense change. The variant allele was found at a frequency of 0.00144 in 1,549,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2152C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 1 hom. )

Consequence

SDK2
NM_001144952.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.49

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SDK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009767026).

BP6

Variant 17-73338651-C-T is Benign according to our data. Variant chr17-73338651-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3052066.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144952.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDK2	NM_001144952.2	MANE Select	c.6455G>A	p.Arg2152His	missense	Exon 45 of 45	NP_001138424.1	Q58EX2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDK2	ENST00000392650.8	TSL:5 MANE Select	c.6455G>A	p.Arg2152His	missense	Exon 45 of 45	ENSP00000376421.3	Q58EX2-1
SDK2	ENST00000424778.1	TSL:5	c.3926G>A	p.Arg1309His	missense	Exon 27 of 27	ENSP00000407098.1	H7C2P2
SDK2	ENST00000410094.5	TSL:5	n.1528G>A		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

151410

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000462

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00585

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000953

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000987

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000848

AC:

169

AN:

199346

AF XY:

0.000816

show subpopulations

Gnomad AFR exome

AF:

0.000726

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000972

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.00146

AC:

2046

AN:

1397630

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

942

AN XY:

689160

show subpopulations

African (AFR)

AF:

0.000258

AC:

AN:

31050

American (AMR)

AF:

0.00268

AC:

AN:

33238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22068

East Asian (EAS)

AF:

0.000128

AC:

AN:

39146

South Asian (SAS)

AF:

0.0000265

AC:

AN:

75456

European-Finnish (FIN)

AF:

0.0000199

AC:

AN:

50246

Middle Eastern (MID)

AF:

0.000184

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.00171

AC:

1853

AN:

1083354

Other (OTH)

AF:

0.00151

AC:

AN:

57632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

188

282

376

470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00120

AC:

182

AN:

151524

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.000461

AC:

AN:

41240

American (AMR)

AF:

0.00584

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000389

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.0000953

AC:

AN:

10494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000987

AC:

AN:

67880

Other (OTH)

AF:

0.00190

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.00212

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000726

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SDK2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.8

PhyloP100

5.5

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.91

REVEL

Benign

0.24

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.45

MVP

0.79

MPC

0.99

ClinPred

0.056

GERP RS

4.8

Varity_R

0.22

gMVP

0.26

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over