20-32031543-T-C

Variant names:

• chr20-32031543-T-C
• rs6121315
• NM_001365692.1:c.*229T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000226239 (HGNC:58356):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365692.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCM2L	NM_001365692.1	MANE Select	c.*229T>C		3_prime_UTR	Exon 10 of 10	NP_001352621.1
	CCM2L	NM_080625.4		c.*579T>C		3_prime_UTR	Exon 9 of 9	NP_542192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCM2L	ENST00000452892.3	TSL:2 MANE Select	c.*229T>C		3_prime_UTR	Exon 10 of 10	ENSP00000392448.2
	CCM2L	ENST00000262659.12	TSL:1	c.*579T>C		3_prime_UTR	Exon 9 of 9	ENSP00000262659.8
	CCM2L	ENST00000953124.1		c.*229T>C		3_prime_UTR	Exon 10 of 10	ENSP00000623183.1

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

African (AFR) AF: 0.605 AC: 1012 AN: 1674

American (AMR) AF: 0.232 AC: 1007 AN: 4338

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 682 AN: 3156

East Asian (EAS) AF: 0.0890 AC: 295 AN: 3314

South Asian (SAS) AF: 0.211 AC: 6226 AN: 29508

European-Finnish (FIN) AF: 0.137 AC: 1120 AN: 8168

Middle Eastern (MID) AF: 0.268 AC: 147 AN: 548

European-Non Finnish (NFE) AF: 0.147 AC: 13513 AN: 91732

Other (OTH) AF: 0.185 AC: 1379 AN: 7448

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

African (AFR) AF: 0.654 AC: 27102 AN: 41464

American (AMR) AF: 0.280 AC: 4287 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3468

East Asian (EAS) AF: 0.117 AC: 603 AN: 5138

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10604

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10596 AN: 67942

Other (OTH) AF: 0.307 AC: 648 AN: 2110

Alfa AF: 0.227 Hom.: 2100

Bravo AF: 0.334

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6121315; hg19: chr20-30619346;