Genetic Variant NM_001326342.2:c.844A>T (chr10-11288420-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001326342.2(CELF2):c.844A>T(p.Met282Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000205 in 1,461,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CELF2
NM_001326342.2 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.79

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20805362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326342.2 link	c.844A>T	p.Met282Leu	missense_variant, splice_region_variant	Exon 9 of 13	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2 link	c.844A>T	p.Met282Leu	missense_variant, splice_region_variant	Exon 9 of 13	1	NM_001326342.2	ENSP00000488690.1		E9PC62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249134

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Benign

0.69

DEOGEN2

Benign

0.0036

T;.;T;T;T;T;.;.;.;.;.;.;.;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;.;D;.;D;D;.;D;D;.;.;D;D;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.58

.;.;.;N;N;.;.;.;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.22

.;.;.;N;.;.;.;N;.;.;N;N;.;.;N

REVEL

Benign

0.26

Sift

Benign

1.0

.;.;.;T;.;.;.;T;.;.;T;T;.;.;T

Sift4G

Benign

1.0

.;.;.;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0, 0.40

.;.;.;B;B;.;B;B;.;.;.;.;.;.;.

Vest4

0.74, 0.74, 0.75, 0.74, 0.74, 0.69, 0.74, 0.74, 0.70, 0.70

MutPred

0.46

.;.;.;.;.;.;Loss of catalytic residue at M282 (P = 0.0626);Loss of catalytic residue at M282 (P = 0.0626);Loss of catalytic residue at M282 (P = 0.0626);.;.;.;.;.;.;

MVP

0.92

ClinPred

0.20

GERP RS

4.8

Varity_R

0.27

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over