rs3780993

Variant names:

• chr10-11273150-G-A
• rs3780993
• NM_001326342.2:c.778-1907G>A

Variant summary

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

The NM_001326342.2(CELF2):​c.778-1907G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 152,104 control chromosomes in the GnomAD database, including 635 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 0.081 (635 hom., cov: 31)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.778-1907G>A		intron_variant	Intron 7 of 12	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.778-1907G>A		intron_variant	Intron 7 of 12	1	NM_001326342.2	ENSP00000488690.1

Frequencies

GnomAD3 genomes AF: 0.0809 AC: 12300 AN: 151986 Hom.: 634 Cov.: 31

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0649

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.0981

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0875

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

GnomAD4 genome AF: 0.0809 AC: 12309 AN: 152104 Hom.: 635 Cov.: 31 AF XY: 0.0810 AC XY: 6021 AN XY: 74352

African (AFR) AF: 0.0241 AC: 1002 AN: 41494

American (AMR) AF: 0.106 AC: 1623 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3470

East Asian (EAS) AF: 0.0654 AC: 337 AN: 5152

South Asian (SAS) AF: 0.0925 AC: 445 AN: 4812

European-Finnish (FIN) AF: 0.0981 AC: 1037 AN: 10572

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6982 AN: 67998

Other (OTH) AF: 0.0885 AC: 187 AN: 2114

Alfa AF: 0.0970 Hom.: 1578

Bravo AF: 0.0811

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.45
PhyloP100		-0.14
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: rs3780993; hg19: chr10-11315113;