chr20-32019047-A-C

Position:

• chr20-32019047-A-C

Variant summary

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

The NM_001365692.1(CCM2L):​c.571A>C​(p.Thr191Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCM2L NM_001365692.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26

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:):

ACMG classification

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	Protein	UniProt
CCM2L	NM_001365692.1	c.571A>C	p.Thr191Pro	missense_variant	5/10	ENST00000452892.3	NP_001352621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCM2L	ENST00000452892.3	c.571A>C	p.Thr191Pro	missense_variant	5/10	2	NM_001365692.1	ENSP00000392448.2
CCM2L	ENST00000262659.12	c.571A>C	p.Thr191Pro	missense_variant	5/9	1		ENSP00000262659.8
ENSG00000226239	ENST00000653258.1	n.704+9881T>G		intron_variant
ENSG00000226239	ENST00000662576.1	n.815+9881T>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

The c.571A>C (p.T191P) alteration is located in exon 5 (coding exon 5) of the CCM2L gene. This alteration results from a A to C substitution at nucleotide position 571, causing the threonine (T) at amino acid position 191 to be replaced by a proline (P). 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	0.068
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Benign	0.97
Eigen	Benign	0.039
Eigen_PC	Benign	-0.011
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.25	T
M_CAP	Pathogenic	0.71	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.28	N
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.27
Sift	Uncertain	0.011	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.17		Loss of phosphorylation at T191 (P = 0.0092);
MVP		0.57
MPC		1.6
ClinPred		0.72	D
GERP RS		2.3
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-30606850;