rs564132631
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_031443.4(CCM2):c.204+2040T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 150,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Consequence
CCM2
NM_031443.4 intron
NM_031443.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.978
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]
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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=-0.89).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000107 (16/150130) while in subpopulation NFE AF= 0.000193 (13/67486). AF 95% confidence interval is 0.000113. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCM2 | NM_031443.4 | c.204+2040T>C | intron_variant | ENST00000258781.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCM2 | ENST00000258781.11 | c.204+2040T>C | intron_variant | 1 | NM_031443.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000107 AC: 16AN: 150130Hom.: 0 Cov.: 33
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?
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.000107 AC: 16AN: 150130Hom.: 0 Cov.: 33 AF XY: 0.000109 AC XY: 8AN XY: 73192
GnomAD4 genome
?
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73192
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Cerebral cavernous malformation 2 Other:1
not provided, no classification provided | research | Institute of Human Genetics Greifswald, Research Division, University Medicine Greifswald | May 15, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at