Genetic Variant ERAP2:p.Ser775Ser (chr5-96909735-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_022350.5(ERAP2):c.2325C>T(p.Ser775Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,613,054 control chromosomes in the GnomAD database, including 219,136 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 22403 hom., cov: 32)

Exomes 𝑓: 0.52 ( 196733 hom. )

Consequence

ERAP2
NM_022350.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.973

Publications

47 publications found

Variant links:

Genes affected

ERAP2 (HGNC:29499): (endoplasmic reticulum aminopeptidase 2) This gene encodes a zinc metalloaminopeptidase of the M1 protease family that resides in the endoplasmic reticulum and functions in N-terminal trimming antigenic epitopes for presentation by major histocompatibility complex (MHC) class I molecules. Certain mutations in this gene are associated with the inflammatory arthritis syndrome ankylosing spondylitis and pre-eclampsia. This gene is located adjacent to a closely related aminopeptidase gene on chromosome 5. [provided by RefSeq, Jul 2016]

ERAP2 links:

ENSG00000247121 (HGNC:):

ENSG00000247121 links:

ERAP1 (HGNC:18173): (endoplasmic reticulum aminopeptidase 1) The protein encoded by this gene is an aminopeptidase involved in trimming HLA class I-binding precursors so that they can be presented on MHC class I molecules. The encoded protein acts as a monomer or as a heterodimer with ERAP2. This protein may also be involved in blood pressure regulation by inactivation of angiotensin II. Three transcript variants encoding two different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]

ERAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-0.973 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERAP2	NM_022350.5 link	c.2325C>T	p.Ser775Ser	synonymous_variant	Exon 15 of 19	ENST00000437043.8	NP_071745.1	Q6P179-1B2R769

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8 link	c.2325C>T	p.Ser775Ser	synonymous_variant	Exon 15 of 19	1	NM_022350.5	ENSP00000400376.3		Q6P179-1

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82357

AN:

151878

Hom.:

22401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.572

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.586

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.555

Gnomad SAS

AF:

0.578

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.541

GnomAD2 exomes

AF:

0.549

AC:

137971

AN:

251146

AF XY:

0.548

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.621

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.588

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.511

Gnomad OTH exome

AF:

0.540

GnomAD4 exome

AF:

0.517

AC:

755718

AN:

1461058

Hom.:

196733

Cov.:

AF XY:

0.519

AC XY:

377147

AN XY:

726846

show subpopulations

African (AFR)

AF:

0.579

AC:

19382

AN:

33458

American (AMR)

AF:

0.619

AC:

27653

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

15708

AN:

26128

East Asian (EAS)

AF:

0.540

AC:

21448

AN:

39686

South Asian (SAS)

AF:

0.587

AC:

50586

AN:

86228

European-Finnish (FIN)

AF:

0.525

AC:

28061

AN:

53402

Middle Eastern (MID)

AF:

0.611

AC:

3521

AN:

5762

European-Non Finnish (NFE)

AF:

0.502

AC:

557918

AN:

1111330

Other (OTH)

AF:

0.521

AC:

31441

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

17610

35220

52829

70439

88049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16366

32732

49098

65464

81830

<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

AF:

0.542

AC:

82394

AN:

151996

Hom.:

22403

Cov.:

AF XY:

0.544

AC XY:

40450

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.571

AC:

23665

AN:

41420

American (AMR)

AF:

0.586

AC:

8948

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

2101

AN:

3464

East Asian (EAS)

AF:

0.555

AC:

2869

AN:

5168

South Asian (SAS)

AF:

0.579

AC:

2793

AN:

4820

European-Finnish (FIN)

AF:

0.531

AC:

5613

AN:

10570

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.510

AC:

34659

AN:

67950

Other (OTH)

AF:

0.536

AC:

1135

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1953

3905

5858

7810

9763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.528

Hom.:

96952

Bravo

AF:

0.553

Asia WGS

AF:

0.488

AC:

1698

AN:

3478

EpiCase

AF:

0.517

EpiControl

AF:

0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.3

(source)

DANN

Benign

0.82

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over