10-11018091-T-A
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001326342.2(CELF2):c.2T>A(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000000752 in 1,330,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 7.5e-7 ( 0 hom. )
Consequence
CELF2
NM_001326342.2 start_lost
NM_001326342.2 start_lost
Scores
3
1
7
Clinical Significance
Conservation
PhyloP100: 3.94
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CELF2 | NM_001326342.2 | c.2T>A | p.Met1? | start_lost | 1/13 | ENST00000633077.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CELF2 | ENST00000633077.2 | c.2T>A | p.Met1? | start_lost | 1/13 | 1 | NM_001326342.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 7.52e-7 AC: 1AN: 1330444Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 662390
GnomAD4 exome
AF:
AC:
1
AN:
1330444
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
662390
Gnomad4 AFR 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
CELF2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 03, 2023 | The CELF2 c.2T>A variant is predicted to disrupt the translation initiation site (p.Met1?). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
B;B;.
Vest4
MutPred
Loss of stability (P = 0.0287);Loss of stability (P = 0.0287);Loss of stability (P = 0.0287);
MVP
0.74
ClinPred
D
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.