Variant chr9-114330004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000608.4(ORM2):c.100G>A(p.Ala34Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,580,566 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000035 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ORM2
NM_000608.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.582

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14037979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORM2	NM_000608.4 linkuse as main transcript	c.100G>A	p.Ala34Thr	missense_variant	1/6	ENST00000431067.4	NP_000599.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORM2	ENST00000431067.4 linkuse as main transcript	c.100G>A	p.Ala34Thr	missense_variant	1/6	1	NM_000608.4	ENSP00000394936	P1

Frequencies

GnomAD3 genomes

AF:

0.0000351

AC:

AN:

142396

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

203482

Hom.:

AF XY:

0.0000364

AC XY:

AN XY:

109980

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000659

Gnomad SAS exome

AF:

0.0000754

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000335

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1438090

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

713942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000715

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000713

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000351

AC:

AN:

142476

Hom.:

Cov.:

AF XY:

0.0000434

AC XY:

AN XY:

69200

show subpopulations

Gnomad4 AFR

AF:

0.000114

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000144

Hom.:

ExAC

AF:

0.0000415

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

Mar 07, 2023

The c.100G>A (p.A34T) alteration is located in exon 1 (coding exon 1) of the ORM2 gene. This alteration results from a G to A substitution at nucleotide position 100, causing the alanine (A) at amino acid position 34 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.024

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.69

M_CAP

Benign

0.0080

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.99

N;N

PROVEAN

Benign

-1.8

REVEL

Benign

0.058

Sift

Benign

0.12

Sift4G

Uncertain

0.055

Polyphen

1.0

Vest4

0.096

MVP

0.33

MPC

1.6

ClinPred

0.072

GERP RS

2.8

Varity_R

0.11

gMVP

0.46

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

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