7-45000353-AG-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_031443.4(CCM2):c.23delG(p.Gly8AlafsTer15) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_031443.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 25
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1139468Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 550080
GnomAD4 genome Cov.: 25
ClinVar
Submissions by phenotype
Cerebral cavernous malformation 2 Pathogenic:2
This sequence change creates a premature translational stop signal (p.Gly8Alafs*15) in the CCM2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CCM2 are known to be pathogenic (PMID: 18300272, 24689081). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with cerebral cavernous malformations (PMID: 14624391). It has also been observed to segregate with disease in related individuals. This variant is also known as 8fsX22. ClinVar contains an entry for this variant (Variation ID: 2680). For these reasons, this variant has been classified as Pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at