rs2549782

Variant summary

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

The ENST00000437043.8(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
ENST00000437043.8 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]

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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

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 P1Q6P179-1
ENST00000501338.5 linkuse as main transcriptn.1689-21918C>G intron_variant, non_coding_transcript_variant 2

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;.;.
MutationTaster
Benign
1.0
P;P;P
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