chr7-45000334-A-G
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_031443.4(CCM2):āc.1A>Gā(p.Met1?) variant causes a start lost 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. Variant has been reported in ClinVar as Pathogenic (ā ā ).
Frequency
Consequence
NM_031443.4 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 25
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000272 AC: 3AN: 1103646Hom.: 0 Cov.: 31 AF XY: 0.00000376 AC XY: 2AN XY: 531494
GnomAD4 genome Cov.: 25
ClinVar
Submissions by phenotype
Cerebral cavernous malformation 2 Pathogenic:2
This sequence change affects the initiator methionine of the CCM2 mRNA. The next in-frame methionine is located at codon 303. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with cerebral cavernous malformations (PMID: 14740320; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2684). This variant disrupts a region of the CCM2 protein in which other variant(s) (p.Leu212Pro) have been determined to be pathogenic (PMID: 27792856; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -
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not provided Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at