Genetic Variant RPN2:p.Leu609Leu (chr20-37236651-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002951.5(RPN2):c.1825C>T(p.Leu609Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 1,613,738 control chromosomes in the GnomAD database, including 500,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45851 hom., cov: 33)

Exomes 𝑓: 0.79 ( 454725 hom. )

Consequence

RPN2
NM_002951.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.401

Publications

30 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 20-37236651-C-T is Benign according to our data. Variant chr20-37236651-C-T is described in ClinVar as Benign. ClinVar VariationId is 683687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.401 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPN2	NM_002951.5 link	c.1825C>T	p.Leu609Leu	synonymous_variant	Exon 16 of 17	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.1825C>T	p.Leu609Leu	synonymous_variant	Exon 16 of 17	1	NM_002951.5	ENSP00000237530.6		P04844-1

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117454

AN:

152054

Hom.:

45826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.776

Gnomad AMI

AF:

0.746

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.840

Gnomad EAS

AF:

0.488

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.810

Gnomad OTH

AF:

0.794

GnomAD2 exomes

AF:

0.740

AC:

185920

AN:

251138

AF XY:

0.746

show subpopulations

Gnomad AFR exome

AF:

0.774

Gnomad AMR exome

AF:

0.674

Gnomad ASJ exome

AF:

0.840

Gnomad EAS exome

AF:

0.474

Gnomad FIN exome

AF:

0.664

Gnomad NFE exome

AF:

0.803

Gnomad OTH exome

AF:

0.788

GnomAD4 exome

AF:

0.786

AC:

1149108

AN:

1461566

Hom.:

454725

Cov.:

AF XY:

0.785

AC XY:

571095

AN XY:

727102

show subpopulations

African (AFR)

AF:

0.777

AC:

26017

AN:

33478

American (AMR)

AF:

0.685

AC:

30626

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.842

AC:

22011

AN:

26132

East Asian (EAS)

AF:

0.533

AC:

21173

AN:

39698

South Asian (SAS)

AF:

0.730

AC:

62963

AN:

86256

European-Finnish (FIN)

AF:

0.672

AC:

35897

AN:

53400

Middle Eastern (MID)

AF:

0.854

AC:

4926

AN:

5768

European-Non Finnish (NFE)

AF:

0.808

AC:

898041

AN:

1111734

Other (OTH)

AF:

0.786

AC:

47454

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

14066

28132

42199

56265

70331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20746

41492

62238

82984

103730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.772

AC:

117528

AN:

152172

Hom.:

45851

Cov.:

AF XY:

0.765

AC XY:

56873

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.776

AC:

32190

AN:

41506

American (AMR)

AF:

0.767

AC:

11739

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.840

AC:

2918

AN:

3472

East Asian (EAS)

AF:

0.488

AC:

2517

AN:

5158

South Asian (SAS)

AF:

0.725

AC:

3498

AN:

4828

European-Finnish (FIN)

AF:

0.656

AC:

6943

AN:

10578

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.810

AC:

55102

AN:

68016

Other (OTH)

AF:

0.794

AC:

1676

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1366

2733

4099

5466

6832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.793

Hom.:

180633

Bravo

AF:

0.779

Asia WGS

AF:

0.655

AC:

2279

AN:

3478

EpiCase

AF:

0.827

EpiControl

AF:

0.821

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital disorder of glycosylation

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.32

CADD

Benign

7.7

(source)

DANN

Benign

0.66

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over