20-37181577-G-C

Variant names:

• chr20-37181577-G-C
• rs6017447
• NM_002951.5:c.13+2208G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002951.5(RPN2):​c.13+2208G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 151,916 control chromosomes in the GnomAD database, including 51,598 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 0.82 (51598 hom., cov: 30)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 3 publications found

Genes affected

RPN2 (HGNC:10382): (ribophorin II) This gene encodes a type I integral membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein is similar in sequence to the yeast oligosaccharyl transferase subunit SWP1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002951.5. 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
	RPN2	NM_002951.5	MANE Select	c.13+2208G>C		intron	N/A	NP_002942.2
	RPN2	NM_001324301.2		c.13+2208G>C		intron	N/A	NP_001311230.1
	RPN2	NM_001324304.2		c.13+2208G>C		intron	N/A	NP_001311233.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.13+2208G>C		intron	N/A	ENSP00000237530.6
	RPN2	ENST00000705448.1		c.13+2208G>C		intron	N/A	ENSP00000516126.1
	RPN2	ENST00000892636.1		c.13+2208G>C		intron	N/A	ENSP00000562695.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124271 AN: 151798 Hom.: 51564 Cov.: 30

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.836

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.819 AC: 124362 AN: 151916 Hom.: 51598 Cov.: 30 AF XY: 0.812 AC XY: 60247 AN XY: 74230

African (AFR) AF: 0.918 AC: 38055 AN: 41470

American (AMR) AF: 0.801 AC: 12230 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2920 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2663 AN: 5126

South Asian (SAS) AF: 0.731 AC: 3524 AN: 4818

European-Finnish (FIN) AF: 0.678 AC: 7137 AN: 10520

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55124 AN: 67928

Other (OTH) AF: 0.835 AC: 1759 AN: 2106

Alfa AF: 0.816 Hom.: 6316

Bravo AF: 0.829

Asia WGS AF: 0.686 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.4
DANN	Benign	0.11
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs6017447; hg19: chr20-35809980;