Genetic Variant CCM2:n.383+304_383+305insGGCCTGCT (chr7-45000161-G-GGGCCTGCT) – 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+305insGGCCTGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0 ( 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:

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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+305insGGCCTGCT	intron	N/A
CCM2	NM_031443.4	MANE Select	c.-173_-172insGGCCTGCT	upstream_gene	N/A	NP_113631.1	Q9BSQ5-1
CCM2	NM_001363458.2		c.-173_-172insGGCCTGCT	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+305insGGCCTGCT	intron	N/A
CCM2	ENST00000258781.11	TSL:1 MANE Select	c.-173_-172insGGCCTGCT	upstream_gene	N/A	ENSP00000258781.7	Q9BSQ5-1
CCM2	ENST00000938553.1		c.-173_-172insGGCCTGCT	upstream_gene	N/A	ENSP00000608612.1

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

113274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000345

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

8946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4554

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:

0.00

AC:

AN:

7328

Other (OTH)

AF:

0.00

AC:

AN:

326

GnomAD4 genome

AF:

0.0000177

AC:

AN:

113274

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

53502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28214

American (AMR)

AF:

0.00

AC:

AN:

10810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3116

East Asian (EAS)

AF:

0.00

AC:

AN:

3746

South Asian (SAS)

AF:

0.00

AC:

AN:

3268

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.0000345

AC:

AN:

57940

Other (OTH)

AF:

0.00

AC:

AN:

1446

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over