Genetic Variant CELF2:c.-71A>T (chr10-10796888-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001326324.2(CELF2):c.-71A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 984,392 control chromosomes in the GnomAD database, including 1,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.035 ( 149 hom., cov: 32)

Exomes 𝑓: 0.052 ( 1215 hom. )

Consequence

CELF2
NM_001326324.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.335

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 10-10796888-A-T is Benign according to our data. Variant chr10-10796888-A-T is described in ClinVar as [Benign]. Clinvar id is 770961.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
CELF2	NM_001326324.2 link	c.-71A>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 15	NP_001313253.1
CELF2	XM_047424484.1 link	c.-70A>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 16	XP_047280440.1
CELF2	XM_047424485.1 link	c.-111A>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	XP_047280441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

AF:

0.0349

AC:

5313

AN:

152210

Hom.:

149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00842

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.0723

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.0523

AC:

43558

AN:

832064

Hom.:

1215

Cov.:

AF XY:

0.0524

AC XY:

20152

AN XY:

384270

show subpopulations

Gnomad4 AFR exome

AF:

0.00608

Gnomad4 AMR exome

AF:

0.0153

Gnomad4 ASJ exome

AF:

0.00563

Gnomad4 EAS exome

AF:

0.000275

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.0870

Gnomad4 NFE exome

AF:

0.0551

Gnomad4 OTH exome

AF:

0.0406

GnomAD4 genome

AF:

0.0349

AC:

5314

AN:

152328

Hom.:

149

Cov.:

AF XY:

0.0349

AC XY:

2596

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00839

Gnomad4 AMR

AF:

0.0207

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0187

Gnomad4 FIN

AF:

0.0723

Gnomad4 NFE

AF:

0.0537

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.0400

Hom.:

Bravo

AF:

0.0306

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.0

DANN

Benign

0.75

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over