17-73338651-C-T

Position:

chr17-73338651-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_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).

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

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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 id is 3052066.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SDK2	NM_001144952.2 linkuse as main transcript	c.6455G>A	p.Arg2152His	missense_variant	45/45	ENST00000392650.8	NP_001138424.1
SDK2	XM_011524914.3 linkuse as main transcript	c.6398G>A	p.Arg2133His	missense_variant	44/44		XP_011523216.1
SDK2	XM_011524915.3 linkuse as main transcript	c.6322+133G>A		intron_variant			XP_011523217.1
SDK2	XM_047436313.1 linkuse as main transcript	c.6265+133G>A		intron_variant			XP_047292269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK2	ENST00000392650.8 linkuse as main transcript	c.6455G>A	p.Arg2152His	missense_variant	45/45	5	NM_001144952.2	ENSP00000376421	P1	Q58EX2-1
SDK2	ENST00000424778.1 linkuse as main transcript	c.3926G>A	p.Arg1309His	missense_variant	27/27	5		ENSP00000407098
SDK2	ENST00000410094.5 linkuse as main transcript	n.1528G>A		non_coding_transcript_exon_variant	10/10	5

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

GnomAD3 exomes

AF:

0.000848

AC:

169

AN:

199346

Hom.:

AF XY:

0.000816

AC XY:

AN XY:

106556

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 SAS 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

Gnomad4 AFR exome

AF:

0.000258

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.0000265

Gnomad4 FIN exome

AF:

0.0000199

Gnomad4 NFE exome

AF:

0.00171

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00120

AC:

182

AN:

151524

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

74038

show subpopulations

Gnomad4 AFR

AF:

0.000461

Gnomad4 AMR

AF:

0.00584

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000953

Gnomad4 NFE

AF:

0.000987

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000961

Hom.:

Bravo

AF:

0.00212

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000726

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SDK2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 05, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.021

T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0098

T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0070

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.45

MVP

0.79

MPC

0.99

ClinPred

0.056

GERP RS

4.8

Varity_R

0.22

gMVP

0.26

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