10-11321249-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001326342.2(CELF2):​c.1157C>G​(p.Thr386Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CELF2
NM_001326342.2 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87
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-AS1 (HGNC:23515): (CELF2 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2940761).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CELF2NM_001326342.2 linkc.1157C>G p.Thr386Arg missense_variant Exon 11 of 13 ENST00000633077.2 NP_001313271.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CELF2ENST00000633077.2 linkc.1157C>G p.Thr386Arg missense_variant Exon 11 of 13 1 NM_001326342.2 ENSP00000488690.1 E9PC62

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Oct 30, 2023
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Uncertain
0.051
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Benign
0.059
T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen
Benign
0.046
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.97
D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.29
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;.;.;L;L;.;.;.;.;.;.;.;.;.;.
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
-1.4
.;.;.;N;.;.;.;N;.;.;N;.;.;.;.
REVEL
Benign
0.13
Sift
Uncertain
0.022
.;.;.;D;.;.;.;T;.;.;T;.;.;.;.
Sift4G
Benign
0.35
.;.;.;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.64, 0.20
.;.;.;P;P;.;B;B;.;.;.;.;.;.;.
Vest4
0.68, 0.67, 0.70, 0.69, 0.69, 0.63, 0.69, 0.69, 0.69, 0.68, 0.58
MutPred
0.43
.;.;.;.;.;.;Gain of solvent accessibility (P = 0.0058);Gain of solvent accessibility (P = 0.0058);.;.;.;.;.;.;.;
MVP
0.62
ClinPred
0.57
D
GERP RS
5.3
Varity_R
0.25
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-11363212; API