rs796342232

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-32019117-C-A
• chr20-32019117-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365692.1(CCM2L):​c.641C>A​(p.Ala214Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 149,428 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A214G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCM2L NM_001365692.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07519755).

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>A	p.Ala214Asp	missense	Exon 5 of 10	NP_001352621.1	Q9NUG4-1
	CCM2L	NM_080625.4		c.641C>A	p.Ala214Asp	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>A	p.Ala214Asp	missense	Exon 5 of 10	ENSP00000392448.2	Q9NUG4-1
	CCM2L	ENST00000262659.12	TSL:1	c.641C>A	p.Ala214Asp	missense	Exon 5 of 9	ENSP00000262659.8	Q9NUG4-2
	CCM2L	ENST00000953124.1		c.641C>A	p.Ala214Asp	missense	Exon 5 of 10	ENSP00000623183.1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149428 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000266

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1013904 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 20154

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 38820

GnomAD4 genome AF: 0.0000268 AC: 4 AN: 149428 Hom.: 0 Cov.: 33 AF XY: 0.0000274 AC XY: 2 AN XY: 72876

African (AFR) AF: 0.00 AC: 0 AN: 40938

American (AMR) AF: 0.000266 AC: 4 AN: 15050

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5100

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67066

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.89
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.077
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.085
Sift	Benign	0.32	T
Sift4G	Uncertain	0.046	D
Polyphen		0.048	B
Vest4		0.20
MutPred		0.28		Gain of catalytic residue at A214 (P = 0.0372)
MVP		0.16
MPC		1.1
ClinPred		0.058	T
GERP RS		2.4
gMVP		0.12
Mutation Taster		=86/14	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;