Variant chr20-32019275-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365692.1(CCM2L):c.799T>C(p.Trp267Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000371 in 1,239,378 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CCM2L
NM_001365692.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCM2L	NM_001365692.1 linkuse as main transcript	c.799T>C	p.Trp267Arg	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.799T>C	p.Trp267Arg	missense_variant	5/10	2	NM_001365692.1	P1	Q9NUG4-1
CCM2L	ENST00000262659.12 linkuse as main transcript	c.799T>C	p.Trp267Arg	missense_variant	5/9	1			Q9NUG4-2
	ENST00000662576.1 linkuse as main transcript	n.815+9653A>G		intron_variant, non_coding_transcript_variant
	ENST00000653258.1 linkuse as main transcript	n.704+9653A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000139

AC:

AN:

150658

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000924

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:

0.0000741

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.000242

AC:

AN:

4136

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

2764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00704

GnomAD4 exome

AF:

0.0000230

AC:

AN:

1088612

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

521856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000446

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000217

Gnomad4 OTH exome

AF:

0.0000228

GnomAD4 genome

AF:

0.000139

AC:

AN:

150766

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73598

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.000923

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000741

Gnomad4 OTH

AF:

0.000480

Bravo

AF:

0.000249

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

Jun 16, 2023

The c.799T>C (p.W267R) alteration is located in exon 5 (coding exon 5) of the CCM2L gene. This alteration results from a T to C substitution at nucleotide position 799, causing the tryptophan (W) at amino acid position 267 to be replaced by an arginine (R). 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

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.59

T;T

M_CAP

Pathogenic

0.99

MetaRNN

Uncertain

0.42

T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.77

D;D

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-2.1

N;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.010

D;T

Sift4G

Benign

0.40

T;D

Polyphen

0.98

D;.

Vest4

0.51

MutPred

0.37

Gain of methylation at W267 (P = 0.0174);.;

MVP

0.63

MPC

1.3

ClinPred

0.14

GERP RS

3.9

gMVP

0.21

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