Variant 9-114330476-G-A 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_000608.4(ORM2):c.157G>A(p.Glu53Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,610,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

ORM2
NM_000608.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.540

Variant links:

Genes affected

ORM2 (HGNC:8499): (orosomucoid 2) This gene encodes a key acute phase plasma protein. Because of its increase due to acute inflammation, this protein is classified as an acute-phase reactant. The specific function of this protein has not yet been determined; however, it may be involved in aspects of immunosuppression. [provided by RefSeq, Jul 2008]

ORM2 links:

AKNA (HGNC:):

AKNA 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=0.051913857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM2	NM_000608.4 linkuse as main transcript	c.157G>A	p.Glu53Lys	missense_variant	2/6	ENST00000431067.4	NP_000599.1
AKNA	XR_929844.4 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORM2	ENST00000431067.4 linkuse as main transcript	c.157G>A	p.Glu53Lys	missense_variant	2/6	1	NM_000608.4	ENSP00000394936	P1

Frequencies

GnomAD3 genomes

AF:

0.0000801

AC:

AN:

149878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.0000917

AC:

AN:

250732

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

178

AN:

1460166

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.0000925

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000145

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000801

AC:

AN:

149878

Hom.:

Cov.:

AF XY:

0.0000547

AC XY:

AN XY:

73184

show subpopulations

Gnomad4 AFR

AF:

0.0000760

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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

Jan 26, 2022

The c.157G>A (p.E53K) alteration is located in exon 2 (coding exon 2) of the ORM2 gene. This alteration results from a G to A substitution at nucleotide position 157, causing the glutamic acid (E) at amino acid position 53 to be replaced by a lysine (K). 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

0.068

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.82

M_CAP

Benign

0.0053

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.090

REVEL

Benign

0.022

Sift

Benign

0.13

Sift4G

Uncertain

0.040

Polyphen

0.40

Vest4

0.25

MVP

0.31

MPC

1.9

ClinPred

0.010

GERP RS

1.2

Varity_R

0.14

gMVP

0.59

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

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