10-11165656-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001326342.2(CELF2):c.245G>A(p.Arg82Gln) 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_001326342.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CELF2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326342.2	c.245G>A	p.Arg82Gln	missense_variant	2/13	ENST00000633077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000633077.2	c.245G>A	p.Arg82Gln	missense_variant	2/13	1	NM_001326342.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 12, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
Cadd	Pathogenic	33
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.035	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	1.0	D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.24	D
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.84	D
Polyphen		1.0	.;.;.;D;D;.;D;D;.;.;.;.;.;.;.
Vest4		0.69, 0.70, 0.71, 0.71, 0.71, 0.74, 0.69, 0.69, 0.67, 0.73
MutPred		0.47		.;.;.;.;.;.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;.;.;.;.;
MVP		0.69
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.95
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-11207619;