10-11005416-T-G

Position:

• chr10-11005416-T-G

Variant summary

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

The NM_001326336.2(CELF2):​c.29T>G​(p.Met10Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CELF2 NM_001326336.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11

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/exons	MANE	Protein	UniProt
CELF2	NM_001326336.2	c.29T>G	p.Met10Arg	missense_variant	1/14		NP_001313265.1
CELF2	NM_001326331.2	c.29T>G	p.Met10Arg	missense_variant	1/14		NP_001313260.1
CELF2	NM_001394502.1	c.29T>G	p.Met10Arg	missense_variant	1/13		NP_001381431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELF2	ENST00000416382.6	c.29T>G	p.Met10Arg	missense_variant	1/13	1		ENSP00000406451.2
CELF2	ENST00000631816.1	c.29T>G	p.Met10Arg	missense_variant	1/14	2		ENSP00000488268.1
CELF2	ENST00000631460.1	c.29T>G	p.Met10Arg	missense_variant	1/14	5		ENSP00000488582.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461648 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

CELF2: PM2, PP2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T;T;T
Eigen	Benign	0.0020
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Benign	0.0	N;N;.
PROVEAN	Benign	-1.1	N;.;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.0040	D;.;.
Sift4G	Benign	0.49	T;T;D
Polyphen		0.12	B;B;.
Vest4		0.83
MutPred		0.31		Loss of catalytic residue at M10 (P = 0.0075);Loss of catalytic residue at M10 (P = 0.0075);Loss of catalytic residue at M10 (P = 0.0075);
MVP		0.98
ClinPred		0.51	D
GERP RS		5.3
Varity_R		0.78

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: chr10-11047379;