Genetic Variant CELF2:p.Thr39Thr (chr10-10919970-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001326325.2(CELF2):c.117G>A(p.Thr39Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,231,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CELF2
NM_001326325.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00500

Publications

0 publications found

Variant links:

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 links:

LINC00710 (HGNC:27386): (long intergenic non-protein coding RNA 710)

LINC00710 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 10-10919970-G-A is Benign according to our data. Variant chr10-10919970-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640298.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.005 with no splicing effect.

BS2

High AC in GnomAd4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
CELF2	NM_001326325.2 link	c.117G>A	p.Thr39Thr	synonymous_variant	Exon 3 of 16	NP_001313254.1
CELF2	NM_001326327.2 link	c.60G>A	p.Thr20Thr	synonymous_variant	Exon 2 of 15	NP_001313256.1
CELF2	NM_001326326.2 link	c.60G>A	p.Thr20Thr	synonymous_variant	Exon 2 of 15	NP_001313255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CELF2	ENST00000637215.1 link	c.60G>A	p.Thr20Thr	synonymous_variant	Exon 2 of 15	5	ENSP00000490185.1	A0A1B0GUN8
CELF2	ENST00000636488.1 link	c.60G>A	p.Thr20Thr	synonymous_variant	Exon 2 of 14	5	ENSP00000489955.1	A0A1B0GU44
CELF2	ENST00000638035.1 link	c.-49G>A		5_prime_UTR_variant	Exon 3 of 15	5	ENSP00000490401.1	O95319-2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

138

AN:

1079240

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

509448

show subpopulations

African (AFR)

AF:

0.000174

AC:

AN:

22966

American (AMR)

AF:

0.000713

AC:

AN:

8418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14390

East Asian (EAS)

AF:

0.00

AC:

AN:

26512

South Asian (SAS)

AF:

0.00

AC:

AN:

19484

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21094

Middle Eastern (MID)

AF:

0.000343

AC:

AN:

2914

European-Non Finnish (NFE)

AF:

0.000130

AC:

120

AN:

919808

Other (OTH)

AF:

0.000160

AC:

AN:

43654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000138

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41526

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000529

Hom.:

Bravo

AF:

0.000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CELF2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

6.3

(source)

DANN

Benign

0.83

PhyloP100

0.0050

Splicing

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

Publications

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10-10919970-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over