10-11270784-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001326342.2(CELF2):c.737A>T(p.Asn246Ile) 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)
• Consequence: CELF2 NM_001326342.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.01

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, CELF2
• BP4: Computational evidence support a benign effect (MetaRNN=0.42048672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326342.2	c.737A>T	p.Asn246Ile	missense_variant	7/13	ENST00000633077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000633077.2	c.737A>T	p.Asn246Ile	missense_variant	7/13	1	NM_001326342.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

CELF2: PM2, PP2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Pathogenic	28
Dann	Uncertain	0.99
DEOGEN2	Benign	0.034	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Benign	0.42	N
LIST_S2	Pathogenic	0.99	D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.42	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.29	D
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
Polyphen		1.0, 0.54	.;.;.;D;D;.;P;P;.;.;.;.;.;.;.
Vest4		0.68, 0.68, 0.67, 0.67, 0.64, 0.67, 0.67, 0.67, 0.66, 0.62, 0.64
MutPred		0.47		.;.;.;.;.;.;Loss of disorder (P = 0.0135);Loss of disorder (P = 0.0135);Loss of disorder (P = 0.0135);.;.;.;.;.;.;
MVP		0.62
ClinPred		0.88	D
GERP RS		5.7
Varity_R		0.55
gMVP		0.66

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: chr10-11312747;