chr10-11005419-G-T

Variant names:

• chr10-11005419-G-T
• ENST00000416382.6:c.32G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001326336.2(CELF2):​c.32G>T​(p.Arg11Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELF2 NM_001326336.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.59
• 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: 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326336.2. 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_001326336.2		c.32G>T	p.Arg11Ile	missense	Exon 1 of 14	NP_001313265.1
	CELF2	NM_001326331.2		c.32G>T	p.Arg11Ile	missense	Exon 1 of 14	NP_001313260.1	A0A0J9YX66
	CELF2	NM_001394502.1		c.32G>T	p.Arg11Ile	missense	Exon 1 of 13	NP_001381431.1	A0A0J9YX66

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000416382.6	TSL:1	c.32G>T	p.Arg11Ile	missense	Exon 1 of 13	ENSP00000406451.2	O95319-1
	CELF2	ENST00000631816.1	TSL:2	c.32G>T	p.Arg11Ile	missense	Exon 1 of 14	ENSP00000488268.1	A0A0J9YX66
	CELF2	ENST00000631460.1	TSL:5	c.32G>T	p.Arg11Ile	missense	Exon 1 of 14	ENSP00000488582.1	O95319-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.6
PROVEAN	Benign	-0.69	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.014	D
Sift4G	Benign	0.11	T
Polyphen		0.86	P
Vest4		0.71
MutPred		0.42		Loss of disorder (P = 0.0049)
MVP		0.87
ClinPred		0.68	D
GERP RS		5.3
PromoterAI		-0.086	Neutral
Varity_R		0.17
Mutation Taster		=71/29	polymorphism

Splicing

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

Other links and lift over

hg19: chr10-11047382; COSMIC: COSV64927778; COSMIC: COSV64927778;