Genetic Variant RPN2:c.14-57C>A (chr20-37184123-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002951.5(RPN2):c.14-57C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,594,134 control chromosomes in the GnomAD database, including 98,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12010 hom., cov: 32)

Exomes 𝑓: 0.34 ( 86111 hom. )

Consequence

RPN2
NM_002951.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.504

Variant links:

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]

RPN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-37184123-C-A is Benign according to our data. Variant chr20-37184123-C-A is described in ClinVar as [Benign]. Clinvar id is 1275370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPN2	NM_002951.5 link	c.14-57C>A		intron_variant	Intron 1 of 16	ENST00000237530.11	NP_002942.2	P04844-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPN2	ENST00000237530.11 link	c.14-57C>A		intron_variant	Intron 1 of 16	1	NM_002951.5	ENSP00000237530.6		P04844-1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57626

AN:

151862

Hom.:

11995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.538

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.388

GnomAD3 exomes

AF:

0.303

AC:

75859

AN:

250236

Hom.:

13284

AF XY:

0.305

AC XY:

41305

AN XY:

135330

show subpopulations

Gnomad AFR exome

AF:

0.537

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.00604

Gnomad SAS exome

AF:

0.265

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.336

AC:

485170

AN:

1442154

Hom.:

86111

Cov.:

AF XY:

0.334

AC XY:

240245

AN XY:

718718

show subpopulations

Gnomad4 AFR exome

AF:

0.539

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.00756

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.340

GnomAD4 genome

AF:

0.379

AC:

57667

AN:

151980

Hom.:

12010

Cov.:

AF XY:

0.372

AC XY:

27619

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.537

Gnomad4 AMR

AF:

0.270

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.00984

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.372

Hom.:

3223

Bravo

AF:

0.383

Asia WGS

AF:

0.166

AC:

579

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.4

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over