Genetic Variant ORM2:p.Ala2Val (chr9-114329909-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000608.4(ORM2):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ORM2
NM_000608.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.185

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15374976).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000608.4. 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
	ORM2	NM_000608.4	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 6	NP_000599.1	P19652

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ORM2	ENST00000431067.4	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000394936.2	P19652
ORM2	ENST00000893195.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 7	ENSP00000563254.1
ORM2	ENST00000893198.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 6	ENSP00000563257.1

Frequencies

GnomAD3 genomes

AF:

0.00000902

AC:

AN:

110848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000323

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000157

AC:

AN:

127292

AF XY:

0.0000300

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000737

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000552

AC:

AN:

1268336

Hom.:

Cov.:

AF XY:

0.00000482

AC XY:

AN XY:

622492

show subpopulations

African (AFR)

AF:

0.0000404

AC:

AN:

24742

American (AMR)

AF:

0.00

AC:

AN:

28496

Ashkenazi Jewish (ASJ)

AF:

0.0000503

AC:

AN:

19886

East Asian (EAS)

AF:

0.0000269

AC:

AN:

37110

South Asian (SAS)

AF:

0.0000288

AC:

AN:

69328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3604

European-Non Finnish (NFE)

AF:

0.00000102

AC:

AN:

983874

Other (OTH)

AF:

0.0000191

AC:

AN:

52406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000902

AC:

AN:

110848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

51862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23148

American (AMR)

AF:

0.00

AC:

AN:

10890

Ashkenazi Jewish (ASJ)

AF:

0.000323

AC:

AN:

3098

East Asian (EAS)

AF:

0.00

AC:

AN:

3796

South Asian (SAS)

AF:

0.00

AC:

AN:

2746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

57746

Other (OTH)

AF:

0.00

AC:

AN:

1374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000171

AC:

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

0.18

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.067

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.51

M_CAP

Benign

0.0064

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.5

PhyloP100

-0.18

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.052

Sift

Uncertain

0.010

Sift4G

Uncertain

0.038

Polyphen

0.89

Vest4

0.19

MutPred

0.35

Gain of sheet (P = 0.0166)

MVP

0.30

MPC

1.5

ClinPred

0.57

GERP RS

-0.21

PromoterAI

-0.069

Neutral

(source)

Varity_R

0.17

gMVP

0.42

Mutation Taster

=97/3

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