20-37184071-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002951.5(RPN2):c.14-109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 1,335,748 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (114 hom.)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0650

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-37184071-C-T is Benign according to our data. Variant chr20-37184071-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1318003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPN2	NM_002951.5	c.14-109C>T		intron_variant		ENST00000237530.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPN2	ENST00000237530.11	c.14-109C>T		intron_variant		1	NM_002951.5	P1

Frequencies

GnomAD3 genomes AF: 0.00754 AC: 1147 AN: 152180 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.00564 AC: 6669 AN: 1183450 Hom.: 114 AF XY: 0.00572 AC XY: 3439 AN XY: 600762

Gnomad4 AFR exome AF: 0.000791

Gnomad4 AMR exome AF: 0.0326

Gnomad4 ASJ exome AF: 0.00161

Gnomad4 EAS exome AF: 0.0567

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.000945

Gnomad4 OTH exome AF: 0.00953

GnomAD4 genome AF: 0.00756 AC: 1152 AN: 152298 Hom.: 23 Cov.: 32 AF XY: 0.00929 AC XY: 692 AN XY: 74466

Gnomad4 AFR AF: 0.00152

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0700

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.00128

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00267 Hom.: 1

Bravo AF: 0.00803

Asia WGS AF: 0.0610 AC: 215 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 23, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.3
Dann	Benign	0.63

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: rs77007680; hg19: chr20-35812474;