10-11013626-T-C

Variant names:

• chr10-11013626-T-C
• rs1547221
• ENST00000416382.6:c.53+8186T>C

Variant summary

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

The ENST00000416382.6(CELF2):​c.53+8186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 152,204 control chromosomes in the GnomAD database, including 58,502 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 0.87 (58502 hom., cov: 32)
• Consequence: CELF2 ENST00000416382.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326325.2	c.146+93627T>C		intron_variant	Intron 3 of 15		NP_001313254.1
CELF2	NM_001326336.2	c.53+8186T>C		intron_variant	Intron 1 of 13		NP_001313265.1
CELF2	NM_001326327.2	c.89+93627T>C		intron_variant	Intron 2 of 14		NP_001313256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000416382.6	c.53+8186T>C		intron_variant	Intron 1 of 12	1		ENSP00000406451.2
CELF2	ENST00000637215.1	c.89+93627T>C		intron_variant	Intron 2 of 14	5		ENSP00000490185.1
CELF2	ENST00000636488.1	c.89+93627T>C		intron_variant	Intron 2 of 13	5		ENSP00000489955.1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132193 AN: 152086 Hom.: 58460 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.979

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.879

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

GnomAD4 genome AF: 0.869 AC: 132289 AN: 152204 Hom.: 58502 Cov.: 32 AF XY: 0.874 AC XY: 65066 AN XY: 74420

African (AFR) AF: 0.689 AC: 28583 AN: 41458

American (AMR) AF: 0.914 AC: 13988 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3198 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5180 AN: 5186

South Asian (SAS) AF: 0.979 AC: 4724 AN: 4824

European-Finnish (FIN) AF: 0.978 AC: 10386 AN: 10618

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63286 AN: 68030

Other (OTH) AF: 0.880 AC: 1860 AN: 2114

Alfa AF: 0.911 Hom.: 102688

Bravo AF: 0.856

Asia WGS AF: 0.981 AC: 3412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.33
PhyloP100		-0.97
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: rs1547221; hg19: chr10-11055589;