10-11005419-G-T

Variant names:

• chr10-11005419-G-T
• ENST00000416382.6:c.32G>T

Variant summary

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

The NM_001326336.2(CELF2):​c.32G>T​(p.Arg11Ile) 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_001326336.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.59

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_001326336.2	c.32G>T	p.Arg11Ile	missense_variant	Exon 1 of 14		NP_001313265.1
CELF2	NM_001326331.2	c.32G>T	p.Arg11Ile	missense_variant	Exon 1 of 14		NP_001313260.1
CELF2	NM_001394502.1	c.32G>T	p.Arg11Ile	missense_variant	Exon 1 of 13		NP_001381431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000416382.6	c.32G>T	p.Arg11Ile	missense_variant	Exon 1 of 13	1		ENSP00000406451.2
CELF2	ENST00000631816.1	c.32G>T	p.Arg11Ile	missense_variant	Exon 1 of 14	2		ENSP00000488268.1
CELF2	ENST00000631460.1	c.32G>T	p.Arg11Ile	missense_variant	Exon 1 of 14	5		ENSP00000488582.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jul 10, 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	Uncertain	0.35
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.079	T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.69	N;N;.
PROVEAN	Benign	-0.69	N;.;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.014	D;.;.
Sift4G	Benign	0.11	T;T;T
Polyphen		0.86	P;P;.
Vest4		0.71
MutPred		0.42		Loss of disorder (P = 0.0049);Loss of disorder (P = 0.0049);Loss of disorder (P = 0.0049);
MVP		0.87
ClinPred		0.68	D
GERP RS		5.3
Varity_R		0.17

Splicing

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: chr10-11047382; COSMIC: COSV64927778; COSMIC: COSV64927778;