Variant 10-11288480-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001326342.2(CELF2):c.904A>G(p.Thr302Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CELF2
NM_001326342.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CELF2. . Trascript score misZ 4.1385 (greater than threshold 3.09). GenCC has associacion of gene with undetermined early-onset epileptic encephalopathy, complex neurodevelopmental disorder, developmental and epileptic encephalopathy 97.

BP4

Computational evidence support a benign effect (MetaRNN=0.2122595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2 linkuse as main transcript	c.904A>G	p.Thr302Ala	missense_variant	9/13	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2 linkuse as main transcript	c.904A>G	p.Thr302Ala	missense_variant	9/13	1	NM_001326342.2	ENSP00000488690	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

May 11, 2022

The c.904A>G (p.T302A) alteration is located in exon 9 (coding exon 9) of the CELF2 gene. This alteration results from a A to G substitution at nucleotide position 904, causing the threonine (T) at amino acid position 302 to be replaced by an alanine (A). 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

0.091

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

T;.;T;T;T;T;.;.;.;.;.;.;.;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

D;.;D;.;D;D;.;D;D;.;.;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;.;.;L;L;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.54

.;.;.;N;.;.;.;N;.;.;N;N;.;.;N

REVEL

Benign

0.089

Sift

Benign

0.26

.;.;.;T;.;.;.;T;.;.;T;T;.;.;T

Sift4G

Benign

0.92

.;.;.;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0010, 0.037

.;.;.;B;B;.;B;B;.;.;.;.;.;.;.

Vest4

0.45, 0.45, 0.46, 0.46, 0.47, 0.48, 0.48, 0.48, 0.47

MutPred

0.28

.;.;.;.;.;.;Loss of glycosylation at T302 (P = 0.0347);Loss of glycosylation at T302 (P = 0.0347);Loss of glycosylation at T302 (P = 0.0347);.;.;.;.;.;.;

MVP

0.46

ClinPred

0.90

GERP RS

4.8

Varity_R

0.056

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over