dbSNP rs201124: CELF2: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 NM_001326325.2(CELF2):c.146+91087A>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
NM_001326325.2 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326325.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
CELF2	NM_001326325.2	c.146+91087A>C	intron	N/A	NP_001313254.1
CELF2	NM_001326336.2	c.53+5646A>C	intron	N/A	NP_001313265.1
CELF2	NM_001326327.2	c.89+91087A>C	intron	N/A	NP_001313256.1	A0A1B0GUN8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CELF2	ENST00000416382.6	TSL:1	c.53+5646A>C	intron	N/A	ENSP00000406451.2	O95319-1
CELF2	ENST00000637215.1	TSL:5	c.89+91087A>C	intron	N/A	ENSP00000490185.1	A0A1B0GUN8
CELF2	ENST00000636488.1	TSL:5	c.89+91087A>C	intron	N/A	ENSP00000489955.1	A0A1B0GU44

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over