10-11255346-T-C

Variant names:

• chr10-11255346-T-C
• rs3740194
• NM_001326342.2:c.404-2392T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001326342.2(CELF2):​c.404-2392T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,946 control chromosomes in the GnomAD database, including 17,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17543 hom., cov: 31)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 4 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.404-2392T>C		intron_variant	Intron 4 of 12	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.404-2392T>C		intron_variant	Intron 4 of 12	1	NM_001326342.2	ENSP00000488690.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71708 AN: 151828 Hom.: 17514 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.472 AC: 71779 AN: 151946 Hom.: 17543 Cov.: 31 AF XY: 0.469 AC XY: 34865 AN XY: 74264

African (AFR) AF: 0.345 AC: 14303 AN: 41430

American (AMR) AF: 0.511 AC: 7808 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1841 AN: 3470

East Asian (EAS) AF: 0.340 AC: 1754 AN: 5156

South Asian (SAS) AF: 0.523 AC: 2517 AN: 4812

European-Finnish (FIN) AF: 0.476 AC: 5023 AN: 10554

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36816 AN: 67940

Other (OTH) AF: 0.492 AC: 1038 AN: 2108

Alfa AF: 0.530 Hom.: 38053

Bravo AF: 0.468

Asia WGS AF: 0.443 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.44
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3740194; hg19: chr10-11297309;