7-45000161-G-GGGCCTGCTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NR_030770.2(CCM2):n.112+304_112+305insGGCCTGCTCT variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (56376 hom., cov: 0)
  • Exomes 𝑓: 0.99 (4423 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCM2 NR_030770.2 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-45000161-G-GGGCCTGCTCT is Benign according to our data. Variant chr7-45000161-G-GGGCCTGCTCT is described in ClinVar as [Benign]. Clinvar id is 1266041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCM2	NM_031443.4			upstream_gene_variant		ENST00000258781.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCM2	ENST00000258781.11			upstream_gene_variant		1	NM_031443.4	P1

Frequencies

GnomAD3 genomes AF: 0.997 AC: 112967 AN: 113264 Hom.: 56339 Cov.: 0

Gnomad AFR AF: 0.997

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.998

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.996

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.994 AC: 8894 AN: 8944 Hom.: 4423 Cov.: 3 AF XY: 0.996 AC XY: 4535 AN XY: 4554

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.992

Gnomad4 FIN exome AF: 0.994

Gnomad4 NFE exome AF: 0.995

Gnomad4 OTH exome AF: 0.991

GnomAD4 genome AF: 0.997 AC: 113040 AN: 113336 Hom.: 56376 Cov.: 0 AF XY: 0.998 AC XY: 53440 AN XY: 53564

Gnomad4 AFR AF: 0.997

Gnomad4 AMR AF: 0.998

Gnomad4 ASJ AF: 0.999

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.997

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3070689; hg19: chr7-45039760;