11-9087740-G-A

Variant names:

• chr11-9087740-G-A
• rs2647528
• NM_001367977.2:c.256+1967C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367977.2(SCUBE2):​c.256+1967C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,122 control chromosomes in the GnomAD database, including 2,567 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2567 hom., cov: 32)
• Consequence: SCUBE2 NM_001367977.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367977.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCUBE2	NM_001367977.2	MANE Select	c.256+1967C>T		intron	N/A	NP_001354906.1
	SCUBE2	NM_001330199.3		c.256+1967C>T		intron	N/A	NP_001317128.1
	SCUBE2	NM_020974.4		c.256+1967C>T		intron	N/A	NP_066025.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCUBE2	ENST00000649792.2	MANE Select	c.256+1967C>T		intron	N/A	ENSP00000497523.1
	SCUBE2	ENST00000450649.6	TSL:1	c.256+1967C>T		intron	N/A	ENSP00000415187.2
	SCUBE2	ENST00000309263.7	TSL:5	c.256+1967C>T		intron	N/A	ENSP00000310658.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27708 AN: 152004 Hom.: 2554 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27735 AN: 152122 Hom.: 2567 Cov.: 32 AF XY: 0.185 AC XY: 13794 AN XY: 74378

African (AFR) AF: 0.175 AC: 7260 AN: 41494

American (AMR) AF: 0.185 AC: 2834 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 840 AN: 3472

East Asian (EAS) AF: 0.186 AC: 960 AN: 5170

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4818

European-Finnish (FIN) AF: 0.163 AC: 1723 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12138 AN: 67974

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.178 Hom.: 6839

Bravo AF: 0.179

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.76
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2647528; hg19: chr11-9109287;