rs10508407

Variant names:

• chr10-10582466-C-A
• rs10508407
• NM_001326319.2:c.-132-99990C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-10582466-C-A
• chr10-10582466-C-G
• chr10-10582466-C-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.-132-99990C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,880 control chromosomes in the GnomAD database, including 7,982 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 (7982 hom., cov: 32)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 1 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

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 (EAS) allele frequency at 95% confidence interval = 0.583 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.-132-99990C>A		intron	N/A	NP_001313248.1
	CELF2	NM_001326323.2		c.-188-99990C>A		intron	N/A	NP_001313252.1
	CELF2	NM_001326321.2		c.-94-99990C>A		intron	N/A	NP_001313250.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47954 AN: 151762 Hom.: 7971 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.316 AC: 48008 AN: 151880 Hom.: 7982 Cov.: 32 AF XY: 0.324 AC XY: 24017 AN XY: 74234

African (AFR) AF: 0.347 AC: 14353 AN: 41398

American (AMR) AF: 0.269 AC: 4107 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3093 AN: 5148

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3618 AN: 10542

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18311 AN: 67922

Other (OTH) AF: 0.315 AC: 666 AN: 2112

Alfa AF: 0.268 Hom.: 2045

Bravo AF: 0.312

Asia WGS AF: 0.478 AC: 1660 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.40
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs10508407; hg19: chr10-10624429;