Variant 2-43224818-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006887.5(ZFP36L2):c.986C>T(p.Ala329Val) variant causes a missense change. The variant allele was found at a frequency of 0.0653 in 1,420,002 control chromosomes in the GnomAD database, including 3,463 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.047 ( 218 hom., cov: 33)

Exomes 𝑓: 0.068 ( 3245 hom. )

Consequence

ZFP36L2
NM_006887.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.02

Variant links:

Genes affected

ZFP36L2 (HGNC:1108): (ZFP36 ring finger protein like 2) This gene is a member of the TIS11 family of early response genes. Family members are induced by various agonists such as the phorbol ester TPA and the polypeptide mitogen EGF. The encoded protein contains a distinguishing putative zinc finger domain with a repeating cys-his motif. This putative nuclear transcription factor most likely functions in regulating the response to growth factors. [provided by RefSeq, Jul 2008]

ZFP36L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017858446).

BP6

Variant 2-43224818-G-A is Benign according to our data. Variant chr2-43224818-G-A is described in ClinVar as [Benign]. Clinvar id is 3056057.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP36L2	NM_006887.5 link	c.986C>T	p.Ala329Val	missense_variant	2/2	ENST00000282388.4	NP_008818.3	P47974

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP36L2	ENST00000282388.4 link	c.986C>T	p.Ala329Val	missense_variant	2/2	1	NM_006887.5	ENSP00000282388.3		P47974

Frequencies

GnomAD3 genomes

AF:

0.0466

AC:

7065

AN:

151708

Hom.:

218

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0745

Gnomad OTH

AF:

0.0441

GnomAD3 exomes

AF:

0.0673

AC:

2017

AN:

29958

Hom.:

AF XY:

0.0646

AC XY:

1192

AN XY:

18458

show subpopulations

Gnomad AFR exome

AF:

0.0202

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0265

Gnomad FIN exome

AF:

0.0417

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0759

GnomAD4 exome

AF:

0.0676

AC:

85711

AN:

1268186

Hom.:

3245

Cov.:

AF XY:

0.0667

AC XY:

41606

AN XY:

623532

show subpopulations

Gnomad4 AFR exome

AF:

0.00877

Gnomad4 AMR exome

AF:

0.0323

Gnomad4 ASJ exome

AF:

0.0983

Gnomad4 EAS exome

AF:

0.000315

Gnomad4 SAS exome

AF:

0.0236

Gnomad4 FIN exome

AF:

0.0335

Gnomad4 NFE exome

AF:

0.0751

Gnomad4 OTH exome

AF:

0.0565

GnomAD4 genome

AF:

0.0465

AC:

7066

AN:

151816

Hom.:

218

Cov.:

AF XY:

0.0431

AC XY:

3202

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0133

Gnomad4 AMR

AF:

0.0331

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.0207

Gnomad4 FIN

AF:

0.0328

Gnomad4 NFE

AF:

0.0745

Gnomad4 OTH

AF:

0.0437

Alfa

AF:

0.0253

Hom.:

Bravo

AF:

0.0448

TwinsUK

AF:

0.0752

AC:

279

ALSPAC

AF:

0.0768

AC:

296

ExAC

AF:

0.0324

AC:

1536

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZFP36L2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 08, 2020

This variant is classified as 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

0.28

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.68

REVEL

Benign

0.088

Sift

Uncertain

0.0090

Sift4G

Benign

0.32

Polyphen

0.63

Vest4

0.30

MPC

0.36

ClinPred

0.039

GERP RS

3.2

Varity_R

0.11

gMVP

0.63

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

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