Genetic Variant NM_002951.5:c.13+21_13+22insATAGACGGGGCCCCGCGGCCGGCACTCTT (chr20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACT) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_002951.5(RPN2):c.13+21_13+22insATAGACGGGGCCCCGCGGCCGGCACTCTT 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0020 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

RPN2
NM_002951.5 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACT is Benign according to our data. Variant chr20-37179387-G-GCTTATAGACGGGGCCCCGCGGCCGGCACT is described in ClinVar as Likely_benign. ClinVar VariationId is 2041031.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPN2	NM_002951.5 link	c.13+21_13+22insATAGACGGGGCCCCGCGGCCGGCACTCTT		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+19insCTTATAGACGGGGCCCCGCGGCCGGCACT		intron_variant	Intron 1 of 16	1	NM_002951.5	ENSP00000237530.6		P04844-1
MROH8	ENST00000343811.10 link	c.92+1_93insAGTGCCGGCCGCGGGGCCCCGTCTATAAG		splice_acceptor_variant, splice_donor_variant, intron_variant	Intron 1 of 24	1		ENSP00000513568.1		A0A8V8TLY2

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

191

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00437

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.00287

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00201

AC:

2730

AN:

1355842

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

1335

AN XY:

663770

show subpopulations

African (AFR)

AF:

0.000389

AC:

AN:

30886

American (AMR)

AF:

0.00233

AC:

AN:

34726

Ashkenazi Jewish (ASJ)

AF:

0.00208

AC:

AN:

24572

East Asian (EAS)

AF:

0.00

AC:

AN:

34844

South Asian (SAS)

AF:

0.00375

AC:

291

AN:

77664

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

35644

Middle Eastern (MID)

AF:

0.000604

AC:

AN:

4968

European-Non Finnish (NFE)

AF:

0.00206

AC:

2180

AN:

1056356

Other (OTH)

AF:

0.00192

AC:

108

AN:

56182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

170

339

509

678

848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.00126

AC:

191

AN:

152008

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41466

American (AMR)

AF:

0.00196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00437

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00171

AC:

116

AN:

67952

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.00134

Hom.:

4465

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation

Benign:1

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

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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