Variant 20-37236651-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
RPN2	NM_002951.5 link	c.1825C>T	p.Leu609Leu	synonymous_variant	16/17	ENST00000237530.11	NP_002942.2	P04844-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPN2	ENST00000237530.11 link	c.1825C>T	p.Leu609Leu	synonymous_variant	16/17	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

GnomAD3 exomes

AF:

0.740

AC:

185920

AN:

251138

Hom.:

70112

AF XY:

0.746

AC XY:

101219

AN XY:

135720

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 SAS exome

AF:

0.734

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

Gnomad4 AFR exome

AF:

0.777

Gnomad4 AMR exome

AF:

0.685

Gnomad4 ASJ exome

AF:

0.842

Gnomad4 EAS exome

AF:

0.533

Gnomad4 SAS exome

AF:

0.730

Gnomad4 FIN exome

AF:

0.672

Gnomad4 NFE exome

AF:

0.808

Gnomad4 OTH exome

AF:

0.786

GnomAD4 genome

AF:

0.772

AC:

117528

AN:

152172

Hom.:

45851

Cov.:

AF XY:

0.765

AC XY:

56873

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.776

Gnomad4 AMR

AF:

0.767

Gnomad4 ASJ

AF:

0.840

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.725

Gnomad4 FIN

AF:

0.656

Gnomad4 NFE

AF:

0.810

Gnomad4 OTH

AF:

0.794

Alfa

AF:

0.798

Hom.:

81834

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

7.7

DANN

Benign

0.66

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