rs10905838

Variant names:

• chr10-10819442-G-A
• rs10905838
• NM_001326325.2:c.16+22539G>A

Variant summary

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

The NM_001326325.2(CELF2):​c.16+22539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 152,108 control chromosomes in the GnomAD database, including 745 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 0.091 (745 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.16+22539G>A		intron_variant	Intron 1 of 15		NP_001313254.1
CELF2	NM_001326327.2	c.53+20625G>A		intron_variant	Intron 1 of 14		NP_001313256.1
CELF2	NM_001326326.2	c.53+20625G>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.53+20625G>A		intron_variant	Intron 1 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.53+20625G>A		intron_variant	Intron 1 of 13	5		ENSP00000489955.1
CELF2	ENST00000638035.1	c.-150+20625G>A		intron_variant	Intron 1 of 14	5		ENSP00000490401.1

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13842 AN: 151990 Hom.: 743 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0743

Gnomad OTH AF: 0.0829

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

GnomAD4 genome AF: 0.0913 AC: 13880 AN: 152108 Hom.: 745 Cov.: 32 AF XY: 0.0960 AC XY: 7139 AN XY: 74350

African (AFR) AF: 0.0849 AC: 3525 AN: 41514

American (AMR) AF: 0.0886 AC: 1354 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1210 AN: 5164

South Asian (SAS) AF: 0.163 AC: 785 AN: 4810

European-Finnish (FIN) AF: 0.147 AC: 1554 AN: 10568

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0743 AC: 5049 AN: 67982

Other (OTH) AF: 0.0839 AC: 177 AN: 2110

Alfa AF: 0.0794 Hom.: 288

Bravo AF: 0.0844

Asia WGS AF: 0.217 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.33
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs10905838; hg19: chr10-10861405;