20-32019117-C-G

Variant names:

• chr20-32019117-C-G
• rs796342232
• NM_001365692.1:c.641C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001365692.1(CCM2L):​c.641C>G​(p.Ala214Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,163,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000087 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: CCM2L NM_001365692.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018897712).

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.641C>G	p.Ala214Gly	missense	Exon 5 of 10	NP_001352621.1	Q9NUG4-1
	CCM2L	NM_080625.4		c.641C>G	p.Ala214Gly	missense	Exon 5 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.641C>G	p.Ala214Gly	missense	Exon 5 of 10	ENSP00000392448.2	Q9NUG4-1
	CCM2L	ENST00000262659.12	TSL:1	c.641C>G	p.Ala214Gly	missense	Exon 5 of 9	ENSP00000262659.8	Q9NUG4-2
	CCM2L	ENST00000953124.1		c.641C>G	p.Ala214Gly	missense	Exon 5 of 10	ENSP00000623183.1

Frequencies

GnomAD3 genomes AF: 0.0000870 AC: 13 AN: 149428 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000533 AC: 54 AN: 1013904 Hom.: 0 Cov.: 28 AF XY: 0.0000753 AC XY: 36 AN XY: 477946

African (AFR) AF: 0.00 AC: 0 AN: 20416

American (AMR) AF: 0.00 AC: 0 AN: 6368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11322

East Asian (EAS) AF: 0.0000496 AC: 1 AN: 20154

South Asian (SAS) AF: 0.00254 AC: 48 AN: 18906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2552

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 876676

Other (OTH) AF: 0.000129 AC: 5 AN: 38820

GnomAD4 genome AF: 0.0000869 AC: 13 AN: 149534 Hom.: 0 Cov.: 33 AF XY: 0.000123 AC XY: 9 AN XY: 72994

African (AFR) AF: 0.00 AC: 0 AN: 41054

American (AMR) AF: 0.00 AC: 0 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9754

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67056

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Benign	0.69
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.32	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.077
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.084
Sift	Benign	0.76	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.22		Loss of stability (P = 0.0343)
MVP		0.072
MPC		0.71
ClinPred		0.036	T
GERP RS		2.4
gMVP		0.096
Mutation Taster		=94/6	polymorphism

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: rs796342232; hg19: chr20-30606920;