rs150503747

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_152744.4(SDK1):c.1255C>G(p.Gln419Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,612,602 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 22 hom., cov: 33)

Exomes 𝑓: 0.012 ( 151 hom. )

Consequence

SDK1
NM_152744.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.48

Publications

6 publications found

Variant links:

Genes affected

SDK1 (HGNC:19307): (sidekick cell adhesion molecule 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

SDK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0108831525).

BP6

Variant 7-3962677-C-G is Benign according to our data. Variant chr7-3962677-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 445721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0106 (1618/152342) while in subpopulation AMR AF = 0.034 (521/15302). AF 95% confidence interval is 0.0316. There are 22 homozygotes in GnomAd4. There are 803 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDK1	NM_152744.4 link	c.1255C>G	p.Gln419Glu	missense_variant	Exon 9 of 45	ENST00000404826.7	NP_689957.3	Q7Z5N4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7 link	c.1255C>G	p.Gln419Glu	missense_variant	Exon 9 of 45	1	NM_152744.4	ENSP00000385899.2		Q7Z5N4-1
SDK1	ENST00000389531.7 link	c.1255C>G	p.Gln419Glu	missense_variant	Exon 9 of 44	5		ENSP00000374182.3		F8W6X9

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1622

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.0106

AC:

2637

AN:

249490

AF XY:

0.0101

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.00413

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0121

GnomAD4 exome

AF:

0.0120

AC:

17553

AN:

1460260

Hom.:

151

Cov.:

AF XY:

0.0114

AC XY:

8272

AN XY:

726354

show subpopulations

African (AFR)

AF:

0.00191

AC:

AN:

33438

American (AMR)

AF:

0.0265

AC:

1177

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.00323

AC:

AN:

25996

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39660

South Asian (SAS)

AF:

0.000348

AC:

AN:

86110

European-Finnish (FIN)

AF:

0.0120

AC:

637

AN:

53298

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0134

AC:

14886

AN:

1111208

Other (OTH)

AF:

0.0109

AC:

659

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

783

1565

2348

3130

3913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

572

1144

1716

2288

2860

<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:

0.0106

AC:

1618

AN:

152342

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

803

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41578

American (AMR)

AF:

0.0340

AC:

521

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0103

AC:

109

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

859

AN:

68036

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

162

243

324

405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0110

Hom.:

Bravo

AF:

0.0117

TwinsUK

AF:

0.0151

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00950

AC:

1153

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0115

EpiControl

AF:

0.0107

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 20, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.026

T;T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.21

N;.;.

PhyloP100

2.5

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.16

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.81

T;T;.

Sift4G

Benign

0.89

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.24

MPC

0.074

ClinPred

0.0057

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.091

gMVP

0.44

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over