chr10-11288420-A-G

Position:

• chr10-11288420-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001326342.2(CELF2):​c.844A>G​(p.Met282Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CELF2 NM_001326342.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.79

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40061957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELF2	NM_001326342.2	c.844A>G	p.Met282Val	missense_variant, splice_region_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.844A>G	p.Met282Val	missense_variant, splice_region_variant	9/13	1	NM_001326342.2	ENSP00000488690.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

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

Apr 28, 2024

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	0.11
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T;.;T;T;T;T;.;.;.;.;.;.;.;T;.
Eigen	Benign	-0.073
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;.;D;.;D;D;.;D;D;.;.;D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	-0.040	.;.;.;N;N;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.60	.;.;.;N;.;.;.;N;.;.;N;N;.;.;N
REVEL	Benign	0.28
Sift	Benign	0.40	.;.;.;T;.;.;.;T;.;.;T;T;.;.;T
Sift4G	Benign	0.44	.;.;.;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.92	.;.;.;B;B;.;P;P;.;.;.;.;.;.;.
Vest4		0.61, 0.61, 0.60, 0.60, 0.61, 0.60, 0.60, 0.59, 0.60
MVP		0.95
ClinPred		0.88	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.80

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

LitVar

Other links and lift over

dbSNP: rs1351416311; hg19: chr10-11330383;