rs2287988

chr5-96901622-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022350.5(ERAP2):c.1689G>A(p.Gln563=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 1,613,618 control chromosomes in the GnomAD database, including 218,582 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 (22344 hom., cov: 32)
  • Exomes 𝑓: 0.52 (196238 hom.)
• Consequence: ERAP2 NM_022350.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.32 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/exons	MANE	UniProt
ERAP2	NM_022350.5	c.1689G>A	p.Gln563=	synonymous_variant	11/19	ENST00000437043.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERAP2	ENST00000437043.8	c.1689G>A	p.Gln563=	synonymous_variant	11/19	1	NM_022350.5	P1
	ENST00000501338.5	n.1689-28244C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82250 AN: 151892 Hom.: 22342 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.539

GnomAD3 exomes AF: 0.548 AC: 137649 AN: 251092 Hom.: 38048 AF XY: 0.547 AC XY: 74220 AN XY: 135724

Gnomad AFR exome AF: 0.576

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.576

Gnomad EAS exome AF: 0.588

Gnomad SAS exome AF: 0.575

Gnomad FIN exome AF: 0.527

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.517 AC: 755105 AN: 1461608 Hom.: 196238 Cov.: 54 AF XY: 0.518 AC XY: 376823 AN XY: 727118

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.618

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.541 AC: 82287 AN: 152010 Hom.: 22344 Cov.: 32 AF XY: 0.544 AC XY: 40382 AN XY: 74286

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.530

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.535

Alfa AF: 0.528 Hom.: 24875

Bravo AF: 0.552

Asia WGS AF: 0.488 AC: 1699 AN: 3478

EpiCase AF: 0.517

EpiControl AF: 0.522

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	2.5
Dann	Benign	0.89

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

Other links and lift over

dbSNP: rs2287988; hg19: chr5-96237326; COSMIC: COSV65939094; COSMIC: COSV65939094;