rs2549794

Variant names:

• chr5-96908845-C-A
• rs2549794
• NM_022350.5:c.2013-116C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-96908845-C-A
• chr5-96908845-C-G
• chr5-96908845-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022350.5(ERAP2):​c.2013-116C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERAP2 NM_022350.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 90 publications found

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]

ENSG00000247121 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022350.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	NM_022350.5	MANE Select	c.2013-116C>A		intron	N/A	NP_071745.1	Q6P179-1
	ERAP2	NM_001130140.3		c.2013-116C>A		intron	N/A	NP_001123612.1
	ERAP2	NM_001437802.1		c.1944-116C>A		intron	N/A	NP_001424731.1	A0AAQ5BHS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERAP2	ENST00000437043.8	TSL:1 MANE Select	c.2013-116C>A		intron	N/A	ENSP00000400376.3	Q6P179-1
	ERAP2	ENST00000379904.8	TSL:1	c.1878-116C>A		intron	N/A	ENSP00000369235.4	Q6P179-3
	ERAP2	ENST00000851668.1		c.2034-116C>A		intron	N/A	ENSP00000521727.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 923788 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 463762

African (AFR) AF: 0.00 AC: 0 AN: 20448

American (AMR) AF: 0.00 AC: 0 AN: 22320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16778

East Asian (EAS) AF: 0.00 AC: 0 AN: 32842

South Asian (SAS) AF: 0.00 AC: 0 AN: 54178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3996

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 690448

Other (OTH) AF: 0.00 AC: 0 AN: 41158

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.30
PhyloP100		-0.97

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

Other links and lift over

dbSNP: rs2549794; hg19: chr5-96244549;