chr10-11036427-T-C

Variant names:

• chr10-11036427-T-C
• rs1999207
• NM_001326342.2:c.74+18264T>C

Variant summary

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

The NM_001326342.2(CELF2):​c.74+18264T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,144 control chromosomes in the GnomAD database, including 14,274 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 0.42 (14274 hom., cov: 33)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• 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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326342.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326342.2	MANE Select	c.74+18264T>C		intron	N/A	NP_001313271.1
	CELF2	NM_001326325.2		c.146+116428T>C		intron	N/A	NP_001313254.1
	CELF2	NM_001326343.2		c.74+18264T>C		intron	N/A	NP_001313272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000633077.2	TSL:1 MANE Select	c.74+18264T>C		intron	N/A	ENSP00000488690.1
	CELF2	ENST00000632065.1	TSL:1	c.74+18264T>C		intron	N/A	ENSP00000488422.1
	CELF2	ENST00000542579.5	TSL:1	c.74+18264T>C		intron	N/A	ENSP00000443926.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64593 AN: 152026 Hom.: 14265 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.425 AC: 64642 AN: 152144 Hom.: 14274 Cov.: 33 AF XY: 0.438 AC XY: 32566 AN XY: 74376

African (AFR) AF: 0.392 AC: 16258 AN: 41504

American (AMR) AF: 0.520 AC: 7956 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1464 AN: 3468

East Asian (EAS) AF: 0.775 AC: 4015 AN: 5180

South Asian (SAS) AF: 0.552 AC: 2655 AN: 4814

European-Finnish (FIN) AF: 0.491 AC: 5193 AN: 10568

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25696 AN: 67994

Other (OTH) AF: 0.433 AC: 916 AN: 2114

Alfa AF: 0.393 Hom.: 37641

Bravo AF: 0.426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.7
DANN	Benign	0.43
PhyloP100		0.065
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1999207; hg19: chr10-11078390;