Variant 10-11288499-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_001326342.2(CELF2):c.923A>G(p.Asn308Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00115 in 1,613,952 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

CELF2
NM_001326342.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.07

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 Benign. Variant got -9 ACMG points.

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=0.012553066).

BP6

Variant 10-11288499-A-G is Benign according to our data. Variant chr10-11288499-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2640299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326342.2 linkuse as main transcript	c.923A>G	p.Asn308Ser	missense_variant	9/13	ENST00000633077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000633077.2 linkuse as main transcript	c.923A>G	p.Asn308Ser	missense_variant	9/13	1	NM_001326342.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000730

AC:

111

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00107

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000835

AC:

208

AN:

249090

Hom.:

AF XY:

0.000805

AC XY:

109

AN XY:

135332

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000976

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00120

AC:

1751

AN:

1461686

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

833

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00142

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.000729

AC:

111

AN:

152266

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00107

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000965

Hom.:

Bravo

AF:

0.000835

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000486

AC:

ESP6500EA

AF:

0.00167

AC:

ExAC

AF:

0.000802

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CELF2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 24, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

CELF2: PP2, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

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

Eigen

Benign

-0.16

Eigen_PC

Benign

0.0026

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.010

MetaRNN

Benign

0.013

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.090

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

REVEL

Benign

0.078

Sift

Benign

0.59

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

Sift4G

Benign

0.88

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

Polyphen

0.0050, 0.0010

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

Vest4

0.35, 0.35, 0.34, 0.35, 0.35, 0.35, 0.35, 0.34

MVP

0.45

ClinPred

0.024

GERP RS

4.8

Varity_R

0.071

gMVP

0.49

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