10-10843919-A-G

Variant summary

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

The NM_001326325.2(CELF2):​c.17-2144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,800 control chromosomes in the GnomAD database, including 43,818 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 0.75 ( 43818 hom., cov: 30)

Consequence

CELF2
NM_001326325.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.09

Publications

0 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

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=-0.98).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELF2NM_001326325.2 linkc.17-2144A>G intron_variant Intron 1 of 15 NP_001313254.1
CELF2NM_001326327.2 linkc.53+45102A>G intron_variant Intron 1 of 14 NP_001313256.1
CELF2NM_001326326.2 linkc.53+45102A>G intron_variant Intron 1 of 14 NP_001313255.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELF2ENST00000637215.1 linkc.53+45102A>G intron_variant Intron 1 of 14 5 ENSP00000490185.1 A0A1B0GUN8
CELF2ENST00000636488.1 linkc.53+45102A>G intron_variant Intron 1 of 13 5 ENSP00000489955.1 A0A1B0GU44
CELF2ENST00000638035.1 linkc.-149-2144A>G intron_variant Intron 1 of 14 5 ENSP00000490401.1 O95319-2

Frequencies

GnomAD3 genomes
AF:
0.754
AC:
114336
AN:
151682
Hom.:
43775
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.876
Gnomad AMI
AF:
0.535
Gnomad AMR
AF:
0.731
Gnomad ASJ
AF:
0.625
Gnomad EAS
AF:
0.971
Gnomad SAS
AF:
0.732
Gnomad FIN
AF:
0.722
Gnomad MID
AF:
0.650
Gnomad NFE
AF:
0.685
Gnomad OTH
AF:
0.724
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.754
AC:
114440
AN:
151800
Hom.:
43818
Cov.:
30
AF XY:
0.755
AC XY:
56030
AN XY:
74174
show subpopulations
African (AFR)
AF:
0.876
AC:
36317
AN:
41468
American (AMR)
AF:
0.732
AC:
11146
AN:
15230
Ashkenazi Jewish (ASJ)
AF:
0.625
AC:
2166
AN:
3468
East Asian (EAS)
AF:
0.971
AC:
5033
AN:
5182
South Asian (SAS)
AF:
0.732
AC:
3524
AN:
4814
European-Finnish (FIN)
AF:
0.722
AC:
7586
AN:
10512
Middle Eastern (MID)
AF:
0.640
AC:
187
AN:
292
European-Non Finnish (NFE)
AF:
0.685
AC:
46457
AN:
67812
Other (OTH)
AF:
0.728
AC:
1536
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1372
2743
4115
5486
6858
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
844
1688
2532
3376
4220
<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:
0.700
Hom.:
22069
Bravo
AF:
0.758

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.0020
DANN
Benign
0.31
PhyloP100
-5.1

Splicing

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

Publications

Other links and lift over

dbSNP: rs968561; hg19: chr10-10885882; API