Genetic Variant ENST00000416382.6:c.53+5646A>C (chr10-11011086-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000416382.6(CELF2):c.53+5646A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,120 control chromosomes in the GnomAD database, including 9,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 9546 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CELF2
ENST00000416382.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.747

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy 97
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CELF2 links:

ENSG00000228027 (HGNC:58359):

ENSG00000228027 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
CELF2-AS4	XR_007062052.1 link	n.171T>G	non_coding_transcript_exon_variant	Exon 1 of 3
CELF2	NM_001326325.2 link	c.146+91087A>C	intron_variant	Intron 3 of 15	NP_001313254.1
CELF2	NM_001326336.2 link	c.53+5646A>C	intron_variant	Intron 1 of 13	NP_001313265.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
CELF2	ENST00000416382.6 link	c.53+5646A>C	intron_variant	Intron 1 of 12	1	ENSP00000406451.2
ENSG00000228027	ENST00000437825.1 link	n.34T>G	non_coding_transcript_exon_variant	Exon 1 of 2	5
CELF2	ENST00000637215.1 link	c.89+91087A>C	intron_variant	Intron 2 of 14	5	ENSP00000490185.1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36615

AN:

152002

Hom.:

9512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.658

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0513

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.0856

Gnomad OTH

AF:

0.205

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.241

AC:

36692

AN:

152120

Hom.:

9546

Cov.:

AF XY:

0.233

AC XY:

17293

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.658

AC:

27251

AN:

41428

American (AMR)

AF:

0.136

AC:

2078

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

446

AN:

3470

East Asian (EAS)

AF:

0.00174

AC:

AN:

5182

South Asian (SAS)

AF:

0.0507

AC:

245

AN:

4828

European-Finnish (FIN)

AF:

0.0253

AC:

268

AN:

10604

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0856

AC:

5824

AN:

68014

Other (OTH)

AF:

0.202

AC:

425

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

894

1788

2681

3575

4469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.115

Hom.:

1408

Bravo

AF:

0.269

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.3

(source)

DANN

Benign

0.82

PhyloP100

0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over