10-11321210-T-C

Position:

• chr10-11321210-T-C

Variant summary

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

The NM_001326342.2(CELF2):​c.1118T>C​(p.Met373Thr) 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: 7.97

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-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.1118T>C	p.Met373Thr	missense_variant	11/13	ENST00000633077.2	NP_001313271.1
CELF2-AS1	NR_126062.1	n.196-2000A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.1118T>C	p.Met373Thr	missense_variant	11/13	1	NM_001326342.2	ENSP00000488690	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Feb 23, 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	0.71
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Benign	0.91
DEOGEN2	Benign	0.016	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Benign	0.075
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;.;D;.;D;D;.;D;T;.;.;D;D;D;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D;D;D;D;D;D;T;T;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	.;.;.;L;L;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.60	.;.;.;N;.;.;.;N;.;.;N;.;.;.;.
REVEL	Uncertain	0.38
Sift	Benign	0.44	.;.;.;T;.;.;.;T;.;.;T;.;.;.;.
Sift4G	Benign	0.44	.;.;.;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.41, 0.039	.;.;.;B;B;.;B;B;.;.;.;.;.;.;.
Vest4		0.80, 0.82, 0.83, 0.83, 0.78, 0.83, 0.83, 0.82, 0.80, 0.79
MutPred		0.50		.;.;.;.;.;.;Gain of glycosylation at M373 (P = 0.0189);Gain of glycosylation at M373 (P = 0.0189);.;.;.;.;.;.;.;
MVP		0.92
ClinPred		0.76	D
GERP RS		5.0
Varity_R		0.19
gMVP		0.95

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: chr10-11363173;