10-10943353-A-G

Variant names:

• chr10-10943353-A-G
• rs1928722
• ENST00000428520.7:n.687+830T>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+23354A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,026 control chromosomes in the GnomAD database, including 8,585 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 0.32 (8585 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 3 publications found

Genes affected

LINC00710 (HGNC:27386): (long intergenic non-protein coding RNA 710)

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

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 = 0.748 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+23354A>G		intron	N/A	NP_001313254.1
	CELF2	NM_001326327.2		c.89+23354A>G		intron	N/A	NP_001313256.1	A0A1B0GUN8
	CELF2	NM_001326326.2		c.89+23354A>G		intron	N/A	NP_001313255.1	A0A1B0GU44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00710	ENST00000428520.7	TSL:1	n.687+830T>C		intron	N/A
	LINC00710	ENST00000635670.2	TSL:1	n.455+830T>C		intron	N/A
	CELF2	ENST00000637215.1	TSL:5	c.89+23354A>G		intron	N/A	ENSP00000490185.1	A0A1B0GUN8

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48166 AN: 151908 Hom.: 8590 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.317 AC: 48173 AN: 152026 Hom.: 8585 Cov.: 32 AF XY: 0.330 AC XY: 24498 AN XY: 74284

African (AFR) AF: 0.226 AC: 9374 AN: 41478

American (AMR) AF: 0.368 AC: 5622 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 935 AN: 3468

East Asian (EAS) AF: 0.768 AC: 3968 AN: 5168

South Asian (SAS) AF: 0.501 AC: 2404 AN: 4798

European-Finnish (FIN) AF: 0.447 AC: 4718 AN: 10550

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20155 AN: 67980

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.310 Hom.: 4204

Bravo AF: 0.310

Asia WGS AF: 0.577 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs1928722; hg19: chr10-10985316;