11-9020784-G-C

Variant names:

• chr11-9020784-G-C
• rs1136966
• NM_001367977.2:c.*261C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367977.2(SCUBE2):​c.*261C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCUBE2 NM_001367977.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 15 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]

NRIP3-DT (HGNC:55524): (NRIP3 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCUBE2	NM_001367977.2	c.*261C>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000649792.2	NP_001354906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCUBE2	ENST00000649792.2	c.*261C>G		3_prime_UTR_variant	Exon 23 of 23		NM_001367977.2	ENSP00000497523.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 148064 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 75514

African (AFR) AF: 0.00 AC: 0 AN: 4896

American (AMR) AF: 0.00 AC: 0 AN: 4494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5898

East Asian (EAS) AF: 0.00 AC: 0 AN: 11572

South Asian (SAS) AF: 0.00 AC: 0 AN: 4544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 788

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 96102

Other (OTH) AF: 0.00 AC: 0 AN: 10044

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.54
PhyloP100		0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1136966; hg19: chr11-9042331;