rs201119

Variant names:

• chr10-11008014-T-C
• rs201119
• ENST00000416382.6:c.53+2574T>C

Variant summary

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

The NM_001326325.2(CELF2):​c.146+88015T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,096 control chromosomes in the GnomAD database, including 9,997 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 0.26 (9997 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326325.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326325.2		c.146+88015T>C		intron	N/A	NP_001313254.1
	CELF2	NM_001326336.2		c.53+2574T>C		intron	N/A	NP_001313265.1
	CELF2	NM_001326327.2		c.89+88015T>C		intron	N/A	NP_001313256.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000416382.6	TSL:1	c.53+2574T>C		intron	N/A	ENSP00000406451.2
	CELF2	ENST00000637215.1	TSL:5	c.89+88015T>C		intron	N/A	ENSP00000490185.1
	CELF2	ENST00000636488.1	TSL:5	c.89+88015T>C		intron	N/A	ENSP00000489955.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39539 AN: 151978 Hom.: 9962 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.0415

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.260 AC: 39618 AN: 152096 Hom.: 9997 Cov.: 32 AF XY: 0.250 AC XY: 18625 AN XY: 74370

African (AFR) AF: 0.662 AC: 27432 AN: 41424

American (AMR) AF: 0.164 AC: 2510 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5190

South Asian (SAS) AF: 0.0575 AC: 277 AN: 4820

European-Finnish (FIN) AF: 0.0415 AC: 440 AN: 10610

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7692 AN: 67984

Other (OTH) AF: 0.228 AC: 482 AN: 2116

Alfa AF: 0.157 Hom.: 5578

Bravo AF: 0.288

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.9
DANN	Benign	0.35
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs201119; hg19: chr10-11049977;