rs1555238867
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_001367977.2(SCUBE2):c.2057G>A(p.Cys686Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SCUBE2
NM_001367977.2 missense
NM_001367977.2 missense
Scores
9
2
1
Clinical Significance
Conservation
PhyloP100: 5.75
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.983
PP5
?
Variant 11-9033742-C-T is Pathogenic according to our data. Variant chr11-9033742-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 545106.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-9033742-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCUBE2 | NM_001367977.2 | c.2057G>A | p.Cys686Tyr | missense_variant | 17/23 | ENST00000649792.2 | |
NRIP3-DT | NR_183663.1 | n.457-25866C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCUBE2 | ENST00000649792.2 | c.2057G>A | p.Cys686Tyr | missense_variant | 17/23 | NM_001367977.2 | P1 | ||
NRIP3-DT | ENST00000670061.1 | n.452-25866C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebral arteriovenous malformation Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital | Feb 14, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
Polyphen
0.96, 1.0
.;D;D
Vest4
1.0, 0.99
MutPred
0.94
.;Loss of disorder (P = 0.065);.;
MVP
0.96
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at