10-11288420-A-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M282V) has been classified as Uncertain significance.

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

Publications

1 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 links:

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

CELF2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326342.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELF2	NM_001326342.2	MANE Select	c.844A>T	p.Met282Leu	missense splice_region	Exon 9 of 13	NP_001313271.1	E9PC62
CELF2	NM_001326325.2		c.916A>T	p.Met306Leu	missense splice_region	Exon 11 of 16	NP_001313254.1
CELF2	NM_001326343.2		c.844A>T	p.Met282Leu	missense splice_region	Exon 9 of 14	NP_001313272.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELF2	ENST00000633077.2	TSL:1 MANE Select	c.844A>T	p.Met282Leu	missense splice_region	Exon 9 of 13	ENSP00000488690.1	E9PC62
CELF2	ENST00000632065.1	TSL:1	c.844A>T	p.Met282Leu	missense splice_region	Exon 9 of 14	ENSP00000488422.1	A0A0J9YXJ0
CELF2	ENST00000542579.5	TSL:1	c.844A>T	p.Met282Leu	missense splice_region	Exon 9 of 14	ENSP00000443926.1	E9PC62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249134

AF XY:

0.00000740

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 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

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0036

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.031

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.58

PhyloP100

6.8

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.22

REVEL

Benign

0.26

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.74

MutPred

0.46

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

Mutation Taster

=65/35

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over