NM_001326342.2:c.112C>G

Variant names:

• chr10-11165523-C-G
• NM_001326342.2:c.112C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001326342.2(CELF2):​c.112C>G​(p.His38Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CELF2 NM_001326342.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.79

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.112C>G	p.His38Asp	missense_variant	Exon 2 of 13	ENST00000633077.2	NP_001313271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000633077.2	c.112C>G	p.His38Asp	missense_variant	Exon 2 of 13	1	NM_001326342.2	ENSP00000488690.1

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

Oct 01, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates 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	Benign	0.26
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.2	.;.;.;L;L;.;.;.;.;.;.;.;.;.;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-2.4	.;.;.;N;.;.;.;N;.;.;N;N;.;.;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	.;.;.;D;.;.;.;D;.;.;D;D;.;.;D
Sift4G	Benign	0.091	.;.;.;T;T;D;T;T;T;D;D;D;D;D;D
Polyphen		0.20, 0.95	.;.;.;B;B;.;P;P;.;.;.;.;.;.;.
Vest4		0.65, 0.65, 0.65, 0.65, 0.65, 0.60, 0.73, 0.73, 0.73, 0.69, 0.68
MutPred		0.28		.;.;.;.;.;.;Gain of phosphorylation at S39 (P = 0.0952);Gain of phosphorylation at S39 (P = 0.0952);Gain of phosphorylation at S39 (P = 0.0952);.;.;.;.;.;.;
MVP		0.74
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.54
gMVP		0.72

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: chr10-11207486;