Variant 11-9027560-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001367977.2(SCUBE2):c.2505C>T(p.Asn835Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,612,158 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00063 ( 7 hom. )

Consequence

SCUBE2
NM_001367977.2 splice_region, synonymous

Scores

Splicing: ADA: 0.006126

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.45

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:

SCUBE2 (HGNC:):

SCUBE2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 11-9027560-G-A is Benign according to our data. Variant chr11-9027560-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025436.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.45 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCUBE2	NM_001367977.2 linkuse as main transcript	c.2505C>T	p.Asn835Asn	splice_region_variant, synonymous_variant	20/23	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.2505C>T	p.Asn835Asn	splice_region_variant, synonymous_variant	20/23		NM_001367977.2	ENSP00000497523.1		A0A3B3ISZ7

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.00602

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00148

AC:

370

AN:

250030

Hom.:

AF XY:

0.00167

AC XY:

226

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00533

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.00728

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.000629

AC:

919

AN:

1459976

Hom.:

Cov.:

AF XY:

0.000809

AC XY:

587

AN XY:

725986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000941

Gnomad4 ASJ exome

AF:

0.00426

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.00724

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000499

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00602

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000467

Hom.:

Bravo

AF:

0.000317

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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

Dec 01, 2023

SCUBE2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0061

dbscSNV1_RF

Benign

0.046

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