NM_001326342.2:c.506G>A

Variant names:

• chr10-11257840-G-A
• rs1390133796
• NM_001326342.2:c.506G>A

Variant summary

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

The NM_001326342.2(CELF2):​c.506G>A​(p.Arg169Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,876 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: 0.0000021 (0 hom.)
• Consequence: CELF2 NM_001326342.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.88
• Publications: 1 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 2 ACMG points.

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

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.506G>A	p.Arg169Gln	missense	Exon 5 of 13	NP_001313271.1	E9PC62
	CELF2	NM_001326325.2		c.578G>A	p.Arg193Gln	missense	Exon 7 of 16	NP_001313254.1
	CELF2	NM_001326343.2		c.506G>A	p.Arg169Gln	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.506G>A	p.Arg169Gln	missense	Exon 5 of 13	ENSP00000488690.1	E9PC62
	CELF2	ENST00000632065.1	TSL:1	c.506G>A	p.Arg169Gln	missense	Exon 5 of 14	ENSP00000488422.1	A0A0J9YXJ0
	CELF2	ENST00000542579.5	TSL:1	c.506G>A	p.Arg169Gln	missense	Exon 5 of 14	ENSP00000443926.1	E9PC62

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

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: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.75
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.028	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		9.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.016	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.72
MutPred		0.45		Gain of catalytic residue at Q164 (P = 0.077)
MVP		0.75
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.54
gMVP		0.84
Mutation Taster		=47/53	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

dbSNP: rs1390133796; hg19: chr10-11299803; COSMIC: COSV59981872;