20-37179610-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.13+241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,046,850 control chromosomes in the GnomAD database, including 1,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (736 hom., cov: 33)
  • Exomes 𝑓: 0.0050 (352 hom.)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0180

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]

MROH8 (HGNC:16125): (maestro heat like repeat family member 8) The protein encoded by this gene belongs to the maestro heat-like repeat family. The exact function of this gene is not known, however, in a genome-wide association study using hippocampal atrophy as a quantitative trait, this gene has been associated with Alzheimer's disease (PMID:19668339). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 20-37179610-C-T is Benign according to our data. Variant chr20-37179610-C-T is described in ClinVar as [Benign]. Clinvar id is 1272265.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPN2	NM_002951.5	c.13+241C>T		intron_variant		ENST00000237530.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPN2	ENST00000237530.11	c.13+241C>T		intron_variant		1	NM_002951.5	P1

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8133 AN: 152162 Hom.: 731 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0444

GnomAD3 exomes AF: 0.0119 AC: 377 AN: 31584 Hom.: 31 AF XY: 0.0109 AC XY: 175 AN XY: 16084

Gnomad AFR exome AF: 0.193

Gnomad AMR exome AF: 0.00965

Gnomad ASJ exome AF: 0.00198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000315

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00901

GnomAD4 exome AF: 0.00497 AC: 4450 AN: 894570 Hom.: 352 Cov.: 12 AF XY: 0.00463 AC XY: 2027 AN XY: 438156

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.000481

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000392

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000398

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0536 AC: 8163 AN: 152280 Hom.: 736 Cov.: 33 AF XY: 0.0518 AC XY: 3856 AN XY: 74466

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0638 Hom.: 80

Bravo AF: 0.0608

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	11
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs79999221; hg19: chr20-35808013;