ENST00000461377.5:n.383+304_383+305insTCCTGCTCT

Variant names:

• chr7-45000161-G-GTCCTGCTCT
• rs3070689
• ENST00000461377.5:n.383+304_383+305insTCCTGCTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000461377.5(CCM2):​n.383+304_383+305insTCCTGCTCT 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 0.00044 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCM2 ENST00000461377.5 intron
• Clinical Significance: Not reported in ClinVar
• 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]

LOC102723334 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000441 (50/113346) while in subpopulation NFE AF= 0.000742 (43/57932). AF 95% confidence interval is 0.000566. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCM2	NM_031443.4	c.-173_-172insTCCTGCTCT		upstream_gene_variant		ENST00000258781.11	NP_113631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCM2	ENST00000258781.11	c.-173_-172insTCCTGCTCT		upstream_gene_variant		1	NM_031443.4	ENSP00000258781.7

Frequencies

GnomAD3 genomes AF: 0.000441 AC: 50 AN: 113274 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000278

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: 0.000742

Gnomad OTH AF: 0.000692

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000559 AC: 5 AN: 8946 Hom.: 0 Cov.: 3 AF XY: 0.000220 AC XY: 1 AN XY: 4554

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000682

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000441 AC: 50 AN: 113346 Hom.: 0 Cov.: 0 AF XY: 0.000336 AC XY: 18 AN XY: 53570

Gnomad4 AFR AF: 0.000106

Gnomad4 AMR AF: 0.000277

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000742

Gnomad4 OTH AF: 0.000684

ClinVar

Not reported in ClinVar

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;