10-11005416-T-G

Variant names:

• chr10-11005416-T-G
• rs747790447
• ENST00000416382.6:c.29T>G

Variant summary

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

The NM_001326336.2(CELF2):​c.29T>G​(p.Met10Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CELF2 NM_001326336.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11
• 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.29T>G	p.Met10Arg	missense	Exon 1 of 14	NP_001313265.1
	CELF2	NM_001326331.2		c.29T>G	p.Met10Arg	missense	Exon 1 of 14	NP_001313260.1	A0A0J9YX66
	CELF2	NM_001394502.1		c.29T>G	p.Met10Arg	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.29T>G	p.Met10Arg	missense	Exon 1 of 13	ENSP00000406451.2	O95319-1
	CELF2	ENST00000631816.1	TSL:2	c.29T>G	p.Met10Arg	missense	Exon 1 of 14	ENSP00000488268.1	A0A0J9YX66
	CELF2	ENST00000631460.1	TSL:5	c.29T>G	p.Met10Arg	missense	Exon 1 of 14	ENSP00000488582.1	O95319-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461648 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111820

Other (OTH) AF: 0.00 AC: 0 AN: 60372

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	Benign	0.15
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.0020
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.0	N
PhyloP100		6.1
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.49	T
Polyphen		0.12	B
Vest4		0.83
MutPred		0.31		Loss of catalytic residue at M10 (P = 0.0075)
MVP		0.98
ClinPred		0.51	D
GERP RS		5.3
PromoterAI		0.051	Neutral
Varity_R		0.78
Mutation Taster		=64/36	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs747790447; hg19: chr10-11047379;