ENST00000461377.5:n.383+304_383+305insTCCTGCTCT
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The ENST00000461377.5(CCM2):n.383+304_383+305insTCCTGCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00044 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00056 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CCM2
ENST00000461377.5 intron
ENST00000461377.5 intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -1.25
Genes affected
CCM2 (HGNC:21708): (CCM2 scaffold protein) This gene encodes a scaffold protein that functions in the stress-activated p38 Mitogen-activated protein kinase (MAPK) signaling cascade. The protein interacts with SMAD specific E3 ubiquitin protein ligase 1 (also known as SMURF1) via a phosphotyrosine binding domain to promote RhoA degradation. The protein is required for normal cytoskeletal structure, cell-cell interactions, and lumen formation in endothelial cells. Mutations in this gene result in cerebral cavernous malformations. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000441 (50/113346) while in subpopulation NFE AF= 0.000742 (43/57932). AF 95% confidence interval is 0.000566. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 50 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000441 AC: 50AN: 113274Hom.: 0 Cov.: 0
GnomAD3 genomes
AF:
AC:
50
AN:
113274
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000559 AC: 5AN: 8946Hom.: 0 Cov.: 3 AF XY: 0.000220 AC XY: 1AN XY: 4554
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
5
AN:
8946
Hom.:
Cov.:
3
AF XY:
AC XY:
1
AN XY:
4554
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000441 AC: 50AN: 113346Hom.: 0 Cov.: 0 AF XY: 0.000336 AC XY: 18AN XY: 53570
GnomAD4 genome
AF:
AC:
50
AN:
113346
Hom.:
Cov.:
0
AF XY:
AC XY:
18
AN XY:
53570
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at