rs2255546

Positions:

• chr5-96913411-C-A
• chr5-96913411-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022350.5(ERAP2):​c.2611C>A​(p.Leu871Ile) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERAP2 NM_022350.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

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]

(HGNC:):

ACMG classification

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=0.23447648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERAP2	NM_022350.5	c.2611C>A	p.Leu871Ile	missense_variant	17/19	ENST00000437043.8	NP_071745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERAP2	ENST00000437043.8	c.2611C>A	p.Leu871Ile	missense_variant	17/19	1	NM_022350.5	ENSP00000400376	P1
	ENST00000501338.5	n.1688+20711G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.034	N
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.60	P;P
Vest4		0.47
MutPred		0.53		Gain of MoRF binding (P = 0.1055);.;
MVP		0.081
MPC		0.34
ClinPred		0.94	D
GERP RS		-3.7
Varity_R		0.45
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs2255546; hg19: chr5-96249115;