10-11018150-G-A

Variant names:

• chr10-11018150-G-A
• NM_001326342.2:c.61G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001326342.2(CELF2):​c.61G>A​(p.Val21Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CELF2 NM_001326342.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.04
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34388846).

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.61G>A	p.Val21Ile	missense	Exon 1 of 13	NP_001313271.1	E9PC62
	CELF2	NM_001326343.2		c.61G>A	p.Val21Ile	missense	Exon 1 of 14	NP_001313272.1
	CELF2	NM_001326340.2		c.61G>A	p.Val21Ile	missense	Exon 1 of 14	NP_001313269.1	A0A0J9YXJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000633077.2	TSL:1 MANE Select	c.61G>A	p.Val21Ile	missense	Exon 1 of 13	ENSP00000488690.1	E9PC62
	CELF2	ENST00000632065.1	TSL:1	c.61G>A	p.Val21Ile	missense	Exon 1 of 14	ENSP00000488422.1	A0A0J9YXJ0
	CELF2	ENST00000542579.5	TSL:1	c.61G>A	p.Val21Ile	missense	Exon 1 of 14	ENSP00000443926.1	E9PC62

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1371016 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682344

African (AFR) AF: 0.00 AC: 0 AN: 27786

American (AMR) AF: 0.00 AC: 0 AN: 34462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23064

East Asian (EAS) AF: 0.00 AC: 0 AN: 29732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064922

Other (OTH) AF: 0.00 AC: 0 AN: 55162

GnomAD4 genome Cov.: 33

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	0.082
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
PhyloP100		7.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.15
Sift	Benign	0.97	T
Sift4G	Benign	0.36	T
Polyphen		0.0050	B
Vest4		0.35
MutPred		0.33		Loss of helix (P = 0.0558)
MVP		0.62
ClinPred		0.95	D
GERP RS		3.2
PromoterAI		-0.0026	Neutral
gMVP		0.098
Mutation Taster		=90/10	polymorphism

Splicing

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

Other links and lift over

hg19: chr10-11060113;