Genetic Variant NM_001326342.2:c.61G>A (chr10-11018150-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001326342.2(CELF2):c.61G>A(p.Val21Ile) 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: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CELF2
NM_001326342.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Publications

0 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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy 97
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CELF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34388846).

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.61G>A	p.Val21Ile	missense	Exon 1 of 13	NP_001313271.1	E9PC62
CELF2	NM_001326343.2		c.61G>A	p.Val21Ile	missense	Exon 1 of 14	NP_001313272.1
CELF2	NM_001326340.2		c.61G>A	p.Val21Ile	missense	Exon 1 of 14	NP_001313269.1	A0A0J9YXJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELF2	ENST00000633077.2	TSL:1 MANE Select	c.61G>A	p.Val21Ile	missense	Exon 1 of 13	ENSP00000488690.1	E9PC62
CELF2	ENST00000632065.1	TSL:1	c.61G>A	p.Val21Ile	missense	Exon 1 of 14	ENSP00000488422.1	A0A0J9YXJ0
CELF2	ENST00000542579.5	TSL:1	c.61G>A	p.Val21Ile	missense	Exon 1 of 14	ENSP00000443926.1	E9PC62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1371016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682344

African (AFR)

AF:

0.00

AC:

AN:

27786

American (AMR)

AF:

0.00

AC:

AN:

34462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23064

East Asian (EAS)

AF:

0.00

AC:

AN:

29732

South Asian (SAS)

AF:

0.00

AC:

AN:

79658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064922

Other (OTH)

AF:

0.00

AC:

AN:

55162

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

PhyloP100

7.0

PromoterAI

-0.0026

Neutral

(source)

gMVP

0.098

Mutation Taster

=90/10

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over