10-11257836-T-A

Variant names:

• chr10-11257836-T-A
• NM_001326342.2:c.502T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001326342.2(CELF2):​c.502T>A​(p.Cys168Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELF2 NM_001326342.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.92
• 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

ENSG00000309976 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

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.502T>A	p.Cys168Ser	missense	Exon 5 of 13	NP_001313271.1	E9PC62
	CELF2	NM_001326325.2		c.574T>A	p.Cys192Ser	missense	Exon 7 of 16	NP_001313254.1
	CELF2	NM_001326343.2		c.502T>A	p.Cys168Ser	missense	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.502T>A	p.Cys168Ser	missense	Exon 5 of 13	ENSP00000488690.1	E9PC62
	CELF2	ENST00000632065.1	TSL:1	c.502T>A	p.Cys168Ser	missense	Exon 5 of 14	ENSP00000488422.1	A0A0J9YXJ0
	CELF2	ENST00000542579.5	TSL:1	c.502T>A	p.Cys168Ser	missense	Exon 5 of 14	ENSP00000443926.1	E9PC62

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-9.1	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.014	D
Polyphen		0.074	B
Vest4		0.83
MutPred		0.76		Gain of disorder (P = 0.0058)
MVP		0.80
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.94
gMVP		0.94
Mutation Taster		=19/81	disease causing

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

hg19: chr10-11299799;