Genetic Variant NM_006887.5:c.1096G>C (chr2-43224708-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006887.5(ZFP36L2):c.1096G>C(p.Gly366Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,381,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G366S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ZFP36L2
NM_006887.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0690

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30877858).

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.1096G>C	p.Gly366Arg	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.1096G>C	p.Gly366Arg	missense	Exon 2 of 2	ENSP00000282388.3	P47974
ZFP36L2	ENST00000929034.1		c.1090G>C	p.Gly364Arg	missense	Exon 2 of 2	ENSP00000599093.1
ZFP36L2	ENST00000929033.1		c.1078G>C	p.Gly360Arg	missense	Exon 2 of 2	ENSP00000599092.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1381890

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

687634

show subpopulations

African (AFR)

AF:

0.0000350

AC:

AN:

28548

American (AMR)

AF:

0.00

AC:

AN:

37148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23872

East Asian (EAS)

AF:

0.00

AC:

AN:

31676

South Asian (SAS)

AF:

0.00

AC:

AN:

79718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5402

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078414

Other (OTH)

AF:

0.00

AC:

AN:

56602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000304

AC:

AN:

3298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.13

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

PhyloP100

-0.069

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.8

REVEL

Benign

0.28

Sift

Uncertain

0.0010

Sift4G

Benign

0.12

Polyphen

0.97

Vest4

0.18

MutPred

0.41

Loss of helix (P = 0.0626)

MVP

0.47

MPC

0.43

ClinPred

0.70

GERP RS

2.2

Varity_R

0.22

gMVP

0.58

Mutation Taster

=85/15

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over