rs2549782

Variant summary

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

The NM_022350.5(ERAP2):​c.1176G>C​(p.Lys392Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 32)

Consequence

ERAP2
NM_022350.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.181
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]
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]

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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=0.020023555).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ERAP2NM_022350.5 linkuse as main transcriptc.1176G>C p.Lys392Asn missense_variant 7/19 ENST00000437043.8 NP_071745.1 Q6P179-1B2R769

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ERAP2ENST00000437043.8 linkuse as main transcriptc.1176G>C p.Lys392Asn missense_variant 7/191 NM_022350.5 ENSP00000400376.3 Q6P179-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
38
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
0.039
DANN
Benign
0.74
DEOGEN2
Benign
0.035
T;T;.
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.67
T;T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.020
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-2.4
N;.;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
5.2
N;N;N
REVEL
Benign
0.067
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;.;B
Vest4
0.10
MutPred
0.30
Gain of catalytic residue at K392 (P = 0.0252);Gain of catalytic residue at K392 (P = 0.0252);.;
MVP
0.061
MPC
0.053
ClinPred
0.051
T
GERP RS
0.68
Varity_R
0.21
gMVP
0.33

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.

Other links and lift over

dbSNP: rs2549782; hg19: chr5-96231000; API