Genetic Variant CCM2:n.383+304_383+305insGGGCCTGCTCT (chr7-45000161-G-GGGGCCTGCTCT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NR_030770.2(CCM2):n.112+304_112+305insGGGCCTGCTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCM2
NR_030770.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

0 publications found

Variant links:

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]

CCM2 Gene-Disease associations (from GenCC):

cerebral cavernous malformation 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
famililal cerebral cavernous malformations
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CCM2 links:

ENSG00000309655 (HGNC:):

ENSG00000309655 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_030770.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCM2	NR_030770.2		n.112+304_112+305insGGGCCTGCTCT	intron	N/A
CCM2	NM_031443.4	MANE Select	c.-173_-172insGGGCCTGCTCT	upstream_gene	N/A	NP_113631.1	Q9BSQ5-1
CCM2	NM_001363458.2		c.-173_-172insGGGCCTGCTCT	upstream_gene	N/A	NP_001350387.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCM2	ENST00000461377.5	TSL:5	n.383+304_383+305insGGGCCTGCTCT	intron	N/A
CCM2	ENST00000258781.11	TSL:1 MANE Select	c.-173_-172insGGGCCTGCTCT	upstream_gene	N/A	ENSP00000258781.7	Q9BSQ5-1
CCM2	ENST00000938553.1		c.-173_-172insGGGCCTGCTCT	upstream_gene	N/A	ENSP00000608612.1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

113274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000185

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00187

Gnomad SAS

AF:

0.000306

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000518

Gnomad OTH

AF:

0.000692

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000224

AC:

AN:

8944

Hom.:

Cov.:

AF XY:

0.000220

AC XY:

AN XY:

4554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

128

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000137

AC:

AN:

7326

Other (OTH)

AF:

0.00307

AC:

AN:

326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000256

AC:

AN:

113346

Hom.:

Cov.:

AF XY:

0.000280

AC XY:

AN XY:

53570

show subpopulations

African (AFR)

AF:

0.000530

AC:

AN:

28288

American (AMR)

AF:

0.000185

AC:

AN:

10828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3116

East Asian (EAS)

AF:

0.00188

AC:

AN:

3732

South Asian (SAS)

AF:

0.000307

AC:

AN:

3262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

172

European-Non Finnish (NFE)

AF:

0.0000518

AC:

AN:

57932

Other (OTH)

AF:

0.000684

AC:

AN:

1462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over