Genetic Variant ZFP36L2:p.Ala377Pro (chr2-43224675-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006887.5(ZFP36L2):c.1129G>C(p.Ala377Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ZFP36L2
NM_006887.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0100

Publications

0 publications found

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:

LINC01126 (HGNC:49275): (long intergenic non-protein coding RNA 1126)

LINC01126 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006887.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP36L2	NM_006887.5	MANE Select	c.1129G>C	p.Ala377Pro	missense	Exon 2 of 2	NP_008818.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP36L2	ENST00000282388.4	TSL:1 MANE Select	c.1129G>C	p.Ala377Pro	missense	Exon 2 of 2	ENSP00000282388.3	P47974
ZFP36L2	ENST00000929034.1		c.1123G>C	p.Ala375Pro	missense	Exon 2 of 2	ENSP00000599093.1
ZFP36L2	ENST00000929033.1		c.1111G>C	p.Ala371Pro	missense	Exon 2 of 2	ENSP00000599092.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

174148

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.21e-7

AC:

AN:

1387518

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28650

American (AMR)

AF:

0.00

AC:

AN:

37824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23964

East Asian (EAS)

AF:

0.00

AC:

AN:

31912

South Asian (SAS)

AF:

0.00

AC:

AN:

80014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5436

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1080152

Other (OTH)

AF:

0.00

AC:

AN:

56836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.91

MetaRNN

Uncertain

0.45

MetaSVM

Benign

-0.56

MutationAssessor

Benign

2.0

PhyloP100

-0.010

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.5

REVEL

Benign

0.20

Sift

Uncertain

0.0030

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.17

MutPred

0.50

Gain of loop (P = 3e-04)

MVP

0.67

MPC

0.47

ClinPred

0.80

GERP RS

3.1

Varity_R

0.59

gMVP

0.67

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over