10-11005437-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Moderate BP6_Moderate BS2

The ENST00000416382.6(CELF2):c.50T>C(p.Leu17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000366 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: CELF2 ENST00000416382.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B: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 Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CELF2
• BP4: Computational evidence support a benign effect (MetaRNN=0.19939512).
• BP6: Variant 10-11005437-T-C is Benign according to our data. Variant chr10-11005437-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3048917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELF2	NM_001326336.2	c.50T>C	p.Leu17Ser	missense_variant	1/14
CELF2	NM_001326331.2	c.50T>C	p.Leu17Ser	missense_variant	1/14
CELF2	NM_001394502.1	c.50T>C	p.Leu17Ser	missense_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELF2	ENST00000416382.6	c.50T>C	p.Leu17Ser	missense_variant	1/13	1
CELF2	ENST00000631816.1	c.50T>C	p.Leu17Ser	missense_variant	1/14	2
CELF2	ENST00000631460.1	c.50T>C	p.Leu17Ser	missense_variant	1/14	5

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000221 AC: 55 AN: 249114 Hom.: 0 AF XY: 0.000200 AC XY: 27 AN XY: 135144

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000345

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000376 AC: 550 AN: 1461614 Hom.: 0 Cov.: 35 AF XY: 0.000380 AC XY: 276 AN XY: 727096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000444

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74364

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000399 Hom.: 0

Bravo AF: 0.000223

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000258 AC: 1

ESP6500EA AF: 0.000848 AC: 7

ExAC AF: 0.000240 AC: 29

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CELF2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 06, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	-0.060
Cadd	Uncertain	23
Dann	Benign	0.94
DEOGEN2	Benign	0.067	T;T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.0016
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.55	N;N;.
MutationTaster	Benign	0.55	N;N
PROVEAN	Benign	0.12	N;.;.
REVEL	Uncertain	0.35
Sift	Benign	0.075	T;.;.
Sift4G	Benign	0.40	T;T;T
Polyphen		0.0080	B;B;.
Vest4		0.64
MVP		0.97
ClinPred		0.041	T
GERP RS		5.3
Varity_R		0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200779130; hg19: chr10-11047400;