Variant 19-13153454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004907.3(IER2):c.268C>T(p.His90Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000037 in 1,595,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

IER2
NM_004907.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0750

Variant links:

Genes affected

IER2 (HGNC:28871): (immediate early response 2) Predicted to enable DNA binding activity. Involved in cell motility and positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IER2 links:

ENSG00000267598 (HGNC:):

ENSG00000267598 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029608548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER2	NM_004907.3 linkuse as main transcript	c.268C>T	p.His90Tyr	missense_variant	2/2	ENST00000292433.4	NP_004898.2	Q9BTL4A0A024R7H1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER2	ENST00000292433.4 linkuse as main transcript	c.268C>T	p.His90Tyr	missense_variant	2/2	1	NM_004907.3	ENSP00000292433.2		Q9BTL4

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000524

AC:

AN:

210082

Hom.:

AF XY:

0.0000777

AC XY:

AN XY:

115814

show subpopulations

Gnomad AFR exome

AF:

0.0000869

Gnomad AMR exome

AF:

0.000157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000627

Gnomad SAS exome

AF:

0.0000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000216

Gnomad OTH exome

AF:

0.000186

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1443276

Hom.:

Cov.:

AF XY:

0.0000223

AC XY:

AN XY:

716994

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000475

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000217

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000849

Hom.:

Bravo

AF:

0.000257

ExAC

AF:

0.00000834

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.268C>T (p.H90Y) alteration is located in exon 2 (coding exon 1) of the IER2 gene. This alteration results from a C to T substitution at nucleotide position 268, causing the histidine (H) at amino acid position 90 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.45

.;.;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.51

.;N;.

REVEL

Benign

0.12

Sift

Uncertain

0.011

.;D;.

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.12

MVP

0.043

MPC

0.50

ClinPred

0.022

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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