Variant chr11-9047368-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001367977.2(SCUBE2):c.1990G>A(p.Glu664Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00227 in 1,614,184 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 13 hom. )

Consequence

SCUBE2
NM_001367977.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

SCUBE2 (HGNC:30425): (signal peptide, CUB domain and EGF like domain containing 2) Predicted to enable calcium ion binding activity; hedgehog family protein binding activity; and lipid binding activity. Predicted to be involved in signal transduction. Predicted to act upstream of or within several processes, including positive regulation of chondrocyte proliferation; positive regulation of osteoblast differentiation; and positive regulation of smoothened signaling pathway. Predicted to be located in extracellular region. Predicted to be active in cell surface and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SCUBE2 links:

NRIP3-DT (HGNC:):

NRIP3-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012090266).

BP6

Variant 11-9047368-C-T is Benign according to our data. Variant chr11-9047368-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641588.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCUBE2	NM_001367977.2 linkuse as main transcript	c.1990G>A	p.Glu664Lys	missense_variant	16/23	ENST00000649792.2	NP_001354906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCUBE2	ENST00000649792.2 linkuse as main transcript	c.1990G>A	p.Glu664Lys	missense_variant	16/23		NM_001367977.2	ENSP00000497523.1		A0A3B3ISZ7

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

218

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00272

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00142

AC:

355

AN:

250048

Hom.:

AF XY:

0.00144

AC XY:

195

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00150

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00249

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00235

AC:

3442

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

1684

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00146

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.00144

GnomAD4 genome

AF:

0.00143

AC:

218

AN:

152296

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00272

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00233

Hom.:

Bravo

AF:

0.00136

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00147

AC:

179

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

SCUBE2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.023

.;T;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.0

.;N;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.0

.;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.38

.;T;T;T

Sift4G

Benign

0.33

.;T;T;T

Polyphen

0.0

.;B;B;B

Vest4

0.20, 0.25, 0.29

MVP

0.80

MPC

0.24

ClinPred

0.019

GERP RS

4.3

Varity_R

0.097

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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