NM_001326319.2:c.-133+82014T>C

Variant names:

• chr10-10544600-T-C
• rs2031339
• NM_001326319.2:c.-133+82014T>C

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+82014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,176 control chromosomes in the GnomAD database, including 8,822 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 0.33 (8822 hom., cov: 34)
• Consequence: CELF2 NM_001326319.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326319.2	c.-133+82014T>C		intron_variant	Intron 1 of 16		NP_001313248.1
CELF2	NM_001326323.2	c.-189+82014T>C		intron_variant	Intron 1 of 17		NP_001313252.1
CELF2	NM_001326321.2	c.-95+82014T>C		intron_variant	Intron 1 of 15		NP_001313250.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49620 AN: 152058 Hom.: 8827 Cov.: 34

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.326 AC: 49623 AN: 152176 Hom.: 8822 Cov.: 34 AF XY: 0.325 AC XY: 24143 AN XY: 74396

African (AFR) AF: 0.204 AC: 8455 AN: 41532

American (AMR) AF: 0.310 AC: 4730 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1300 AN: 3468

East Asian (EAS) AF: 0.152 AC: 787 AN: 5178

South Asian (SAS) AF: 0.291 AC: 1408 AN: 4832

European-Finnish (FIN) AF: 0.397 AC: 4209 AN: 10590

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27461 AN: 67976

Other (OTH) AF: 0.339 AC: 716 AN: 2112

Alfa AF: 0.377 Hom.: 5449

Bravo AF: 0.313

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.48
PhyloP100		-0.042

Splicing

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

Other links and lift over

dbSNP: rs2031339; hg19: chr10-10586563;