rs624964

Variant names:

• chr10-11189868-A-G
• rs624964
• NM_001326342.2:c.271+24186A>G

Variant summary

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

The NM_001326342.2(CELF2):​c.271+24186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,104 control chromosomes in the GnomAD database, including 11,582 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 0.38 (11582 hom., cov: 32)
• Consequence: CELF2 NM_001326342.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• 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: 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

LOC124902375 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326342.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326342.2	MANE Select	c.271+24186A>G		intron	N/A	NP_001313271.1
	CELF2	NM_001326325.2		c.343+24186A>G		intron	N/A	NP_001313254.1
	CELF2	NM_001326343.2		c.271+24186A>G		intron	N/A	NP_001313272.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000633077.2	TSL:1 MANE Select	c.271+24186A>G		intron	N/A	ENSP00000488690.1
	CELF2	ENST00000632065.1	TSL:1	c.271+24186A>G		intron	N/A	ENSP00000488422.1
	CELF2	ENST00000542579.5	TSL:1	c.271+24186A>G		intron	N/A	ENSP00000443926.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57516 AN: 151986 Hom.: 11576 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.378 AC: 57567 AN: 152104 Hom.: 11582 Cov.: 32 AF XY: 0.386 AC XY: 28692 AN XY: 74378

African (AFR) AF: 0.442 AC: 18328 AN: 41476

American (AMR) AF: 0.452 AC: 6904 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1112 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3480 AN: 5180

South Asian (SAS) AF: 0.538 AC: 2590 AN: 4818

European-Finnish (FIN) AF: 0.314 AC: 3319 AN: 10582

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20763 AN: 67978

Other (OTH) AF: 0.370 AC: 779 AN: 2108

Alfa AF: 0.337 Hom.: 26203

Bravo AF: 0.390

Asia WGS AF: 0.586 AC: 2038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.48
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs624964; hg19: chr10-11231831;