10-11257772-A-T

Variant names:

• chr10-11257772-A-T
• rs2277212
• NM_001326342.2:c.438A>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001326342.2(CELF2):​c.438A>T​(p.Val146Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 1,613,594 control chromosomes in the GnomAD database, including 456,737 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 0.74 (42033 hom., cov: 33)
  • Exomes 𝑓: 0.75 (414704 hom.)
• Consequence: CELF2 NM_001326342.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 21 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

ENSG00000309976 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=1.66 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326342.2	MANE Select	c.438A>T	p.Val146Val	synonymous	Exon 5 of 13	NP_001313271.1	E9PC62
	CELF2	NM_001326325.2		c.510A>T	p.Val170Val	synonymous	Exon 7 of 16	NP_001313254.1
	CELF2	NM_001326343.2		c.438A>T	p.Val146Val	synonymous	Exon 5 of 14	NP_001313272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000633077.2	TSL:1 MANE Select	c.438A>T	p.Val146Val	synonymous	Exon 5 of 13	ENSP00000488690.1	E9PC62
	CELF2	ENST00000632065.1	TSL:1	c.438A>T	p.Val146Val	synonymous	Exon 5 of 14	ENSP00000488422.1	A0A0J9YXJ0
	CELF2	ENST00000542579.5	TSL:1	c.438A>T	p.Val146Val	synonymous	Exon 5 of 14	ENSP00000443926.1	E9PC62

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112940 AN: 152086 Hom.: 41995 Cov.: 33

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.743

GnomAD2 exomes AF: 0.754 AC: 188218 AN: 249494 AF XY: 0.758

Gnomad AFR exome AF: 0.740

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.676

Gnomad EAS exome AF: 0.847

Gnomad FIN exome AF: 0.739

Gnomad NFE exome AF: 0.741

Gnomad OTH exome AF: 0.752

GnomAD4 exome AF: 0.753 AC: 1099920 AN: 1461390 Hom.: 414704 Cov.: 40 AF XY: 0.754 AC XY: 548475 AN XY: 727016

African (AFR) AF: 0.741 AC: 24789 AN: 33472

American (AMR) AF: 0.721 AC: 32231 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 17697 AN: 26126

East Asian (EAS) AF: 0.854 AC: 33908 AN: 39694

South Asian (SAS) AF: 0.829 AC: 71469 AN: 86242

European-Finnish (FIN) AF: 0.737 AC: 39386 AN: 53412

Middle Eastern (MID) AF: 0.738 AC: 4251 AN: 5764

European-Non Finnish (NFE) AF: 0.748 AC: 831056 AN: 1111600

Other (OTH) AF: 0.748 AC: 45133 AN: 60368

GnomAD4 genome AF: 0.743 AC: 113034 AN: 152204 Hom.: 42033 Cov.: 33 AF XY: 0.745 AC XY: 55432 AN XY: 74408

African (AFR) AF: 0.742 AC: 30791 AN: 41520

American (AMR) AF: 0.702 AC: 10744 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2362 AN: 3472

East Asian (EAS) AF: 0.846 AC: 4386 AN: 5182

South Asian (SAS) AF: 0.835 AC: 4030 AN: 4824

European-Finnish (FIN) AF: 0.735 AC: 7787 AN: 10590

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50471 AN: 68000

Other (OTH) AF: 0.745 AC: 1573 AN: 2112

Alfa AF: 0.737 Hom.: 13443

Bravo AF: 0.741

Asia WGS AF: 0.822 AC: 2855 AN: 3478

EpiCase AF: 0.741

EpiControl AF: 0.738

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.9
DANN	Benign	0.87
PhyloP100		1.7
Mutation Taster		=94/6	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: rs2277212; hg19: chr10-11299735; COSMIC: COSV107329453;