rs2224693

Variant names:

• chr10-10881888-T-A
• rs2224693
• NM_001326325.2:c.110+35732T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-10881888-T-A
• chr10-10881888-T-C
• chr10-10881888-T-G

Variant summary

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

The NM_001326325.2(CELF2):​c.110+35732T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,114 control chromosomes in the GnomAD database, including 30,529 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 0.62 (30529 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.110+35732T>A		intron_variant	Intron 2 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.54-38076T>A		intron_variant	Intron 1 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.54-38076T>A		intron_variant	Intron 1 of 14		NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000637215.1	c.54-38076T>A		intron_variant	Intron 1 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.54-38076T>A		intron_variant	Intron 1 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-56+35732T>A		intron_variant	Intron 2 of 14	5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93901 AN: 151998 Hom.: 30474 Cov.: 32

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.618 AC: 94017 AN: 152114 Hom.: 30529 Cov.: 32 AF XY: 0.626 AC XY: 46575 AN XY: 74360

African (AFR) AF: 0.779 AC: 32319 AN: 41498

American (AMR) AF: 0.626 AC: 9566 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3468

East Asian (EAS) AF: 0.972 AC: 5045 AN: 5190

South Asian (SAS) AF: 0.674 AC: 3249 AN: 4824

European-Finnish (FIN) AF: 0.603 AC: 6368 AN: 10566

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34343 AN: 67976

Other (OTH) AF: 0.582 AC: 1232 AN: 2116

Alfa AF: 0.570 Hom.: 3170

Bravo AF: 0.627

Asia WGS AF: 0.838 AC: 2910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.36
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs2224693; hg19: chr10-10923851;