chr10-11270793-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_001326342.2(CELF2):c.746G>T(p.Gly249Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CELF2
NM_001326342.2 missense
NM_001326342.2 missense
Scores
7
5
2
Clinical Significance
Conservation
PhyloP100: 10.0
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CELF2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.755
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CELF2 | NM_001326342.2 | c.746G>T | p.Gly249Val | missense_variant | 7/13 | ENST00000633077.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CELF2 | ENST00000633077.2 | c.746G>T | p.Gly249Val | missense_variant | 7/13 | 1 | NM_001326342.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1359420Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 673076
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1359420
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
673076
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy 97 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology | Jun 05, 2023 | The c.746G>T variant is not present in publicly available population databases like 1000 Genomes, ExAC, EVS, gnomAD, Indian Exome Database or our in-house exome database. This variant has neither been published in literature nor reported to clinical databases like in ClinVar, Human Gene Mutation Database (HGMD) or OMIM, in any affected individuals. In silico pathogenicity prediction programs like PolyPhen2, MutationTaster2, CADD, etc predicted this variant to be likely deleterious, however these predictions were not confirmed by published functional studies. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
Polyphen
1.0, 1.0
.;.;.;D;D;.;D;D;.;.;.;.;.;.;.
Vest4
0.86, 0.86, 0.85, 0.86, 0.85, 0.81, 0.85, 0.85, 0.86, 0.80, 0.81
MutPred
0.49
.;.;.;.;.;.;Loss of disorder (P = 0.0206);Loss of disorder (P = 0.0206);Loss of disorder (P = 0.0206);.;.;.;.;.;.;
MVP
0.94
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.