Genetic Variant NM_006887.5:c.1307G>C (chr2-43224497-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006887.5(ZFP36L2):c.1307G>C(p.Arg436Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,341,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ZFP36L2
NM_006887.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13106194).

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.1307G>C	p.Arg436Pro	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.1307G>C	p.Arg436Pro	missense	Exon 2 of 2	ENSP00000282388.3	P47974
ZFP36L2	ENST00000929034.1		c.1301G>C	p.Arg434Pro	missense	Exon 2 of 2	ENSP00000599093.1
ZFP36L2	ENST00000929033.1		c.1289G>C	p.Arg430Pro	missense	Exon 2 of 2	ENSP00000599092.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000224

AC:

AN:

1341956

Hom.:

Cov.:

AF XY:

0.00000302

AC XY:

AN XY:

662304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27382

American (AMR)

AF:

0.00

AC:

AN:

31016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23812

East Asian (EAS)

AF:

0.00

AC:

AN:

29284

South Asian (SAS)

AF:

0.00

AC:

AN:

76004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35252

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.00000283

AC:

AN:

1059434

Other (OTH)

AF:

0.00

AC:

AN:

55700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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.:

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

Benign

0.14

BayesDel_addAF

Benign

-0.093

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.039

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.53

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.9

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.56

REVEL

Benign

0.17

Sift

Benign

0.37

Sift4G

Benign

0.38

Polyphen

0.066

Vest4

0.25

MutPred

0.20

Loss of stability (P = 0.0322)

MVP

0.45

MPC

0.53

ClinPred

0.33

GERP RS

3.7

Varity_R

0.30

gMVP

0.43

Mutation Taster

=61/39

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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