10-11288480-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001326342.2(CELF2):c.904A>G(p.Thr302Ala) 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: 6.75

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 1 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=0.2122595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326342.2	c.904A>G	p.Thr302Ala	missense_variant	9/13	ENST00000633077.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000633077.2	c.904A>G	p.Thr302Ala	missense_variant	9/13	1	NM_001326342.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.904A>G (p.T302A) alteration is located in exon 9 (coding exon 9) of the CELF2 gene. This alteration results from a A to G substitution at nucleotide position 904, causing the threonine (T) at amino acid position 302 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	24
Dann	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.026
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.49	T
Polyphen		0.0010, 0.037	.;.;.;B;B;.;B;B;.;.;.;.;.;.;.
Vest4		0.45, 0.45, 0.46, 0.46, 0.47, 0.48, 0.48, 0.48, 0.47
MutPred		0.28		.;.;.;.;.;.;Loss of glycosylation at T302 (P = 0.0347);Loss of glycosylation at T302 (P = 0.0347);Loss of glycosylation at T302 (P = 0.0347);.;.;.;.;.;.;
MVP		0.46
ClinPred		0.90	D
GERP RS		4.8
Varity_R		0.056
gMVP		0.53

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: chr10-11330443;