Genetic Variant RPN2:c.13+21_13+22insATAGACAGGGCCCCGCGGCCAGCACTCTT (chr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCAGCACT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002951.5(RPN2):c.13+21_13+22insATAGACAGGGCCCCGCGGCCAGCACTCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RPN2
NM_002951.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.659

Publications

9 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:

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]

MROH8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPN2	NM_002951.5 link	c.13+21_13+22insATAGACAGGGCCCCGCGGCCAGCACTCTT		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.13+18_13+19insCTTATAGACAGGGCCCCGCGGCCAGCACT		intron_variant	Intron 1 of 16	1	NM_002951.5	ENSP00000237530.6		P04844-1
MROH8	ENST00000343811.10 link	c.92+1_93insAGTGCTGGCCGCGGGGCCCTGTCTATAAG		splice_acceptor_variant, splice_donor_variant, intron_variant	Intron 1 of 24	1		ENSP00000513568.1		A0A8V8TLY2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000148

AC:

AN:

1355842

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

663772

show subpopulations

African (AFR)

AF:

0.000550

AC:

AN:

30886

American (AMR)

AF:

0.00

AC:

AN:

34726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24572

East Asian (EAS)

AF:

0.00

AC:

AN:

34844

South Asian (SAS)

AF:

0.0000258

AC:

AN:

77664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4968

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1056358

Other (OTH)

AF:

0.0000178

AC:

AN:

56182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000395

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67960

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

4465

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.66

Mutation Taster

=36/64

disease causing

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over