10-10508250-A-T

Variant names:

• chr10-10508250-A-T
• rs980994
• NM_001326319.2:c.-133+45664A>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+45664A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,874 control chromosomes in the GnomAD database, including 26,171 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 0.58 (26171 hom., cov: 31)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 0 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

ENSG00000296415 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326319.2	c.-133+45664A>T		intron_variant	Intron 1 of 16		NP_001313248.1
CELF2	NM_001326323.2	c.-189+45664A>T		intron_variant	Intron 1 of 17		NP_001313252.1
CELF2	NM_001326321.2	c.-95+45664A>T		intron_variant	Intron 1 of 15		NP_001313250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000296415	ENST00000739530.1	n.173+8682T>A		intron_variant	Intron 2 of 2
ENSG00000289363	ENST00000690687.1	n.*68A>T		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88385 AN: 151754 Hom.: 26144 Cov.: 31

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.582 AC: 88461 AN: 151874 Hom.: 26171 Cov.: 31 AF XY: 0.591 AC XY: 43882 AN XY: 74196

African (AFR) AF: 0.558 AC: 23076 AN: 41390

American (AMR) AF: 0.644 AC: 9831 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2284 AN: 3470

East Asian (EAS) AF: 0.886 AC: 4566 AN: 5152

South Asian (SAS) AF: 0.647 AC: 3111 AN: 4808

European-Finnish (FIN) AF: 0.621 AC: 6519 AN: 10502

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37118 AN: 67968

Other (OTH) AF: 0.592 AC: 1247 AN: 2108

Alfa AF: 0.575 Hom.: 3159

Bravo AF: 0.584

Asia WGS AF: 0.754 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.37
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs980994; hg19: chr10-10550213;