10-11329003-C-G

Position:

• chr10-11329003-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001326342.2(CELF2):​c.1516C>G​(p.Arg506Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CELF2 NM_001326342.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.93

Genes affected

CELF2 (HGNC:2550): (CUGBP Elav-like family member 2) Members of the CELF/BRUNOL protein family contain two N-terminal RNA recognition motif (RRM) domains, one C-terminal RRM domain, and a divergent segment of 160-230 aa between the second and third RRM domains. Members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing, and translation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

CELF2-AS1 (HGNC:23515): (CELF2 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.768
• PP5: Variant 10-11329003-C-G is Pathogenic according to our data. Variant chr10-11329003-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1299464.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-11329003-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.1516C>G	p.Arg506Gly	missense_variant	13/13	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.1516C>G	p.Arg506Gly	missense_variant	13/13	1	NM_001326342.2	ENSP00000488690.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental and epileptic encephalopathy 97 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	30
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.98	D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.77	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	.;.;.;M;M;.;.;.;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.5	.;.;.;D;.;.;.;D;.;.;D;.;.;.;.
REVEL	Uncertain	0.40
Sift	Uncertain	0.0010	.;.;.;D;.;.;.;D;.;.;D;.;.;.;.
Sift4G	Pathogenic	0.0	.;.;.;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.77, 0.95	.;.;.;P;P;.;P;P;.;.;.;.;.;.;.
Vest4		0.83, 0.87, 0.87, 0.86, 0.88, 0.84, 0.83, 0.83, 0.87, 0.87, 0.84
MutPred		0.62		.;.;.;.;.;.;Loss of MoRF binding (P = 0.0587);Loss of MoRF binding (P = 0.0587);.;.;.;.;.;.;.;
MVP		0.83
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.87
gMVP		0.97

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: chr10-11370966;