Variant 20-32019117-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 14/20 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0770

Variant links:

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]

CCM2L links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCM2L	NM_001365692.1 linkuse as main transcript	c.641C>G	p.Ala214Gly	missense_variant	5/10	ENST00000452892.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCM2L	ENST00000452892.3 linkuse as main transcript	c.641C>G	p.Ala214Gly	missense_variant	5/10	2	NM_001365692.1	P1	Q9NUG4-1
CCM2L	ENST00000262659.12 linkuse as main transcript	c.641C>G	p.Ala214Gly	missense_variant	5/9	1			Q9NUG4-2
	ENST00000662576.1 linkuse as main transcript	n.815+9811G>C		intron_variant, non_coding_transcript_variant
	ENST00000653258.1 linkuse as main transcript	n.704+9811G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000870

AC:

AN:

149428

Hom.:

Cov.:

show subpopulations

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:

AN:

1013904

Hom.:

Cov.:

AF XY:

0.0000753

AC XY:

AN XY:

477946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000496

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000129

GnomAD4 genome

AF:

0.0000869

AC:

AN:

149534

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

72994

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.641C>G (p.A214G) alteration is located in exon 5 (coding exon 5) of the CCM2L gene. This alteration results from a C to G substitution at nucleotide position 641, causing the alanine (A) at amino acid position 214 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.69

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.46

REVEL

Benign

0.084

Sift

Benign

0.76

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.074

MutPred

0.22

Loss of stability (P = 0.0343);

MVP

0.072

MPC

0.71

ClinPred

0.036

GERP RS

2.4

gMVP

0.096

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over