10-11288543-A-T

Position:

• chr10-11288543-A-T

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.967A>T​(p.Thr323Ser) 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. 12/21 in silico tools predict 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: Not reported in ClinVar
• Conservation: PhyloP100: 6.81

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 in gene, where missense usually causes diseases (based on misZ statistic), CELF2. . Trascript score misZ 4.1385 (greater than threshold 3.09). GenCC has associacion of gene with undetermined early-onset epileptic encephalopathy, complex neurodevelopmental disorder, developmental and epileptic encephalopathy 97.
• BP4: Computational evidence support a benign effect (MetaRNN=0.24702683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.967A>T	p.Thr323Ser	missense_variant	9/13	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.967A>T	p.Thr323Ser	missense_variant	9/13	1	NM_001326342.2	ENSP00000488690	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Benign	-0.055
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T;.;D;.;D;T;.;T;T;.;.;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;.;.;L;L;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.0	.;.;.;N;.;.;.;N;.;.;N;N;.;.;N
REVEL	Benign	0.077
Sift	Benign	0.17	.;.;.;T;.;.;.;T;.;.;T;T;.;.;T
Sift4G	Benign	0.34	.;.;.;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.28, 0.0080	.;.;.;B;B;.;B;B;.;.;.;.;.;.;.
Vest4		0.38, 0.37, 0.39, 0.38, 0.37, 0.43, 0.37, 0.38, 0.42
MutPred		0.22		.;.;.;.;.;.;Gain of glycosylation at T323 (P = 0.022);Gain of glycosylation at T323 (P = 0.022);Gain of glycosylation at T323 (P = 0.022);.;.;.;.;.;.;
MVP		0.47
ClinPred		0.89	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.37

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: chr10-11330506;