10-10515910-G-T

Variant names:

• chr10-10515910-G-T
• rs1000039
• NM_001326319.2:c.-133+53324G>T

Variant summary

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

The NM_001326319.2(CELF2):​c.-133+53324G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 152,202 control chromosomes in the GnomAD database, including 465 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 0.062 (465 hom., cov: 32)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000296415 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326319.2. 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_001326319.2		c.-133+53324G>T		intron	N/A	NP_001313248.1
	CELF2	NM_001326323.2		c.-189+53324G>T		intron	N/A	NP_001313252.1
	CELF2	NM_001326321.2		c.-95+53324G>T		intron	N/A	NP_001313250.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000296415	ENST00000739530.1		n.173+1022C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9425 AN: 152084 Hom.: 468 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0333

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0517

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

GnomAD4 genome AF: 0.0620 AC: 9430 AN: 152202 Hom.: 465 Cov.: 32 AF XY: 0.0583 AC XY: 4335 AN XY: 74412

African (AFR) AF: 0.137 AC: 5697 AN: 41500

American (AMR) AF: 0.0332 AC: 508 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3468

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5186

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4832

European-Finnish (FIN) AF: 0.0271 AC: 287 AN: 10592

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2473 AN: 68014

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0423 Hom.: 283

Bravo AF: 0.0670

Asia WGS AF: 0.0420 AC: 146 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs1000039; hg19: chr10-10557873;