10-11288420-A-G

Variant names:

• chr10-11288420-A-G
• rs1351416311
• NM_001326342.2:c.844A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 publications found

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:23515): (CELF2 antisense RNA 1) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001326342.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	NM_001326342.2	MANE Select	c.844A>G	p.Met282Val	missense splice_region	Exon 9 of 13	NP_001313271.1	E9PC62
	CELF2	NM_001326325.2		c.916A>G	p.Met306Val	missense splice_region	Exon 11 of 16	NP_001313254.1
	CELF2	NM_001326343.2		c.844A>G	p.Met282Val	missense splice_region	Exon 9 of 14	NP_001313272.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELF2	ENST00000633077.2	TSL:1 MANE Select	c.844A>G	p.Met282Val	missense splice_region	Exon 9 of 13	ENSP00000488690.1	E9PC62
	CELF2	ENST00000632065.1	TSL:1	c.844A>G	p.Met282Val	missense splice_region	Exon 9 of 14	ENSP00000488422.1	A0A0J9YXJ0
	CELF2	ENST00000542579.5	TSL:1	c.844A>G	p.Met282Val	missense splice_region	Exon 9 of 14	ENSP00000443926.1	E9PC62

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.073
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	-0.040	N
PhyloP100		6.8
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.28
Sift	Benign	0.40	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.61
MVP		0.95
ClinPred		0.88	D
GERP RS		4.8
Varity_R		0.19
gMVP		0.80
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs1351416311; hg19: chr10-11330383;