10-10982786-G-A

Variant names:

• chr10-10982786-G-A
• rs201100
• NM_001326325.2:c.146+62787G>A

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+62787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,106 control chromosomes in the GnomAD database, including 38,920 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 0.70 (38920 hom., cov: 32)
• Consequence: CELF2 NM_001326325.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 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+62787G>A		intron	N/A	NP_001313254.1
	CELF2	NM_001326327.2		c.89+62787G>A		intron	N/A	NP_001313256.1	A0A1B0GUN8
	CELF2	NM_001326326.2		c.89+62787G>A		intron	N/A	NP_001313255.1	A0A1B0GU44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000637215.1	TSL:5	c.89+62787G>A		intron	N/A	ENSP00000490185.1	A0A1B0GUN8
	CELF2	ENST00000636488.1	TSL:5	c.89+62787G>A		intron	N/A	ENSP00000489955.1	A0A1B0GU44
	CELF2	ENST00000638035.1	TSL:5	c.-20+62787G>A		intron	N/A	ENSP00000490401.1	O95319-2

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106278 AN: 151988 Hom.: 38847 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.700 AC: 106410 AN: 152106 Hom.: 38920 Cov.: 32 AF XY: 0.705 AC XY: 52415 AN XY: 74356

African (AFR) AF: 0.912 AC: 37871 AN: 41518

American (AMR) AF: 0.722 AC: 11028 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2098 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4299 AN: 5178

South Asian (SAS) AF: 0.675 AC: 3250 AN: 4818

European-Finnish (FIN) AF: 0.679 AC: 7175 AN: 10564

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38500 AN: 67966

Other (OTH) AF: 0.684 AC: 1442 AN: 2108

Alfa AF: 0.621 Hom.: 23378

Bravo AF: 0.714

Asia WGS AF: 0.761 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.69
DANN	Benign	0.40
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs201100; hg19: chr10-11024749;