rs2477037

Variant names:

• chr10-10491192-G-C
• rs2477037
• NM_001326319.2:c.-133+28606G>C

Variant summary

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

The NM_001326319.2(CELF2):​c.-133+28606G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,960 control chromosomes in the GnomAD database, including 10,563 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 0.36 (10563 hom., cov: 32)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 0 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

ENSG00000296415 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326319.2	c.-133+28606G>C		intron_variant	Intron 1 of 16		NP_001313248.1
CELF2	NM_001326323.2	c.-189+28606G>C		intron_variant	Intron 1 of 17		NP_001313252.1
CELF2	NM_001326321.2	c.-95+28606G>C		intron_variant	Intron 1 of 15		NP_001313250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296415	ENST00000739530.1	n.174-3616C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54572 AN: 151842 Hom.: 10548 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.359 AC: 54625 AN: 151960 Hom.: 10563 Cov.: 32 AF XY: 0.364 AC XY: 27045 AN XY: 74282

African (AFR) AF: 0.222 AC: 9197 AN: 41476

American (AMR) AF: 0.516 AC: 7884 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.411 AC: 2123 AN: 5164

South Asian (SAS) AF: 0.432 AC: 2083 AN: 4822

European-Finnish (FIN) AF: 0.439 AC: 4630 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26324 AN: 67904

Other (OTH) AF: 0.383 AC: 808 AN: 2110

Alfa AF: 0.360 Hom.: 1269

Bravo AF: 0.362

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs2477037; hg19: chr10-10533155;