Variant rs2304689 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031443.4(CCM2):c.205-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,443,514 control chromosomes in the GnomAD database, including 35,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3818 hom., cov: 31)

Exomes 𝑓: 0.22 ( 31669 hom. )

Consequence

CCM2
NM_031443.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.908

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 7-45063882-A-G is Benign according to our data. Variant chr7-45063882-A-G is described in ClinVar as [Benign]. Clinvar id is 261967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCM2	NM_031443.4 linkuse as main transcript	c.205-36A>G		intron_variant		ENST00000258781.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCM2	ENST00000258781.11 linkuse as main transcript	c.205-36A>G		intron_variant		1	NM_031443.4	P1	Q9BSQ5-1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

33992

AN:

151360

Hom.:

3813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.230

AC:

57695

AN:

250714

Hom.:

7109

AF XY:

0.223

AC XY:

30173

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.358

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.197

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.218

AC:

281121

AN:

1292036

Hom.:

31669

Cov.:

AF XY:

0.216

AC XY:

140664

AN XY:

652286

show subpopulations

Gnomad4 AFR exome

AF:

0.255

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.206

Gnomad4 NFE exome

AF:

0.215

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.225

AC:

34027

AN:

151478

Hom.:

3818

Cov.:

AF XY:

0.224

AC XY:

16575

AN XY:

73958

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.215

Hom.:

632

Bravo

AF:

0.233

Asia WGS

AF:

0.197

AC:

688

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.0

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over