rs557904216
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_031443.4(CCM2):c.30+17G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000661 in 1,286,624 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 Benign (★).
Frequency
Genomes: 𝑓 0.000088 ( 0 hom., cov: 24)
Exomes 𝑓: 0.000063 ( 0 hom. )
Consequence
CCM2
NM_031443.4 intron
NM_031443.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.30
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 7-45000380-G-T is Benign according to our data. Variant chr7-45000380-G-T is described in ClinVar as [Benign]. Clinvar id is 261969.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000885 (13/146974) while in subpopulation SAS AF= 0.00279 (13/4654). AF 95% confidence interval is 0.00165. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
BS2
?
High AC in GnomAd at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCM2 | NM_031443.4 | c.30+17G>T | intron_variant | ENST00000258781.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCM2 | ENST00000258781.11 | c.30+17G>T | intron_variant | 1 | NM_031443.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000885 AC: 13AN: 146874Hom.: 0 Cov.: 24
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GnomAD3 exomes AF: 0.000393 AC: 16AN: 40754Hom.: 0 AF XY: 0.000576 AC XY: 13AN XY: 22572
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GnomAD4 exome AF: 0.0000632 AC: 72AN: 1139650Hom.: 0 Cov.: 31 AF XY: 0.0000802 AC XY: 44AN XY: 548770
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GnomAD4 genome ? AF: 0.0000885 AC: 13AN: 146974Hom.: 0 Cov.: 24 AF XY: 0.000168 AC XY: 12AN XY: 71404
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 20, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at