chr20-32031543-T-C

Position:

• chr20-32031543-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365692.1(CCM2L):​c.*229T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 301,932 control chromosomes in the GnomAD database, including 13,423 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (10858 hom., cov: 32)
  • Exomes 𝑓: 0.17 (2565 hom.)
• Consequence: CCM2L NM_001365692.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.27

Genes affected

CCM2L (HGNC:16153): (CCM2 like scaffold protein) Predicted to act upstream of or within several processes, including heart development; negative regulation of homotypic cell-cell adhesion; and positive regulation of fibroblast growth factor production. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCM2L	NM_001365692.1	c.*229T>C		3_prime_UTR_variant	10/10	ENST00000452892.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCM2L	ENST00000452892.3	c.*229T>C		3_prime_UTR_variant	10/10	2	NM_001365692.1	P1
	ENST00000662576.1	n.10A>G		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46585 AN: 151926 Hom.: 10814 Cov.: 32

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.169 AC: 25381 AN: 149886 Hom.: 2565 Cov.: 0 AF XY: 0.175 AC XY: 14203 AN XY: 81206

Gnomad4 AFR exome AF: 0.605

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.0890

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.307 AC: 46688 AN: 152046 Hom.: 10858 Cov.: 32 AF XY: 0.303 AC XY: 22508 AN XY: 74322

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.307

Alfa AF: 0.218 Hom.: 1616

Bravo AF: 0.334

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs6121315; hg19: chr20-30619346;