Genetic Variant ENST00000416382.6:c.50T>C (chr10-11005437-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The ENST00000416382.6(CELF2):c.50T>C(p.Leu17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000366 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

CELF2
ENST00000416382.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.11

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19939512).

BP6

Variant 10-11005437-T-C is Benign according to our data. Variant chr10-11005437-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3048917.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
CELF2	NM_001326336.2 link	c.50T>C	p.Leu17Ser	missense_variant	Exon 1 of 14	NP_001313265.1
CELF2	NM_001326331.2 link	c.50T>C	p.Leu17Ser	missense_variant	Exon 1 of 14	NP_001313260.1
CELF2	NM_001394502.1 link	c.50T>C	p.Leu17Ser	missense_variant	Exon 1 of 13	NP_001381431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CELF2	ENST00000416382.6 link	c.50T>C	p.Leu17Ser	missense_variant	Exon 1 of 13	1	ENSP00000406451.2	O95319-1
CELF2	ENST00000631816.1 link	c.50T>C	p.Leu17Ser	missense_variant	Exon 1 of 14	2	ENSP00000488268.1	A0A0J9YX66
CELF2	ENST00000631460.1 link	c.50T>C	p.Leu17Ser	missense_variant	Exon 1 of 14	5	ENSP00000488582.1	O95319-1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000221

AC:

AN:

249114

Hom.:

AF XY:

0.000200

AC XY:

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000345

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000376

AC:

550

AN:

1461614

Hom.:

Cov.:

AF XY:

0.000380

AC XY:

276

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000444

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000269

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000399

Hom.:

Bravo

AF:

0.000223

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000258

AC:

ESP6500EA

AF:

0.000848

AC:

ExAC

AF:

0.000240

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CELF2-related disorder

Benign:1

May 06, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.067

T;T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

0.0016

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.59

.;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.55

N;N;.

PROVEAN

Benign

0.12

N;.;.

REVEL

Uncertain

0.35

Sift

Benign

0.075

T;.;.

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0080

B;B;.

Vest4

0.64

MVP

0.97

ClinPred

0.041

GERP RS

5.3

Varity_R

0.10

Splicing

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