chr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACT

Variant names:

• chr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACT
• rs11467214
• NM_002951.5:c.13+21_13+22insATAGACAGGGCCCCGCGGCCGGCACTCTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002951.5(RPN2):​c.13+21_13+22insATAGACAGGGCCCCGCGGCCGGCACTCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 1,507,500 control chromosomes in the GnomAD database, including 483,994 homozygotes. 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 0.82 (52352 hom., cov: 0)
  • Exomes 𝑓: 0.80 (431642 hom.)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.659
• Publications: 9 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACT is Benign according to our data. Variant chr20-37179387-G-GCTTATAGACAGGGCCCCGCGGCCGGCACT is described in ClinVar as Likely_benign. ClinVar VariationId is 1115482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPN2	NM_002951.5	c.13+21_13+22insATAGACAGGGCCCCGCGGCCGGCACTCTT		intron_variant	Intron 1 of 16	ENST00000237530.11	NP_002942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPN2	ENST00000237530.11	c.13+18_13+19insCTTATAGACAGGGCCCCGCGGCCGGCACT		intron_variant	Intron 1 of 16	1	NM_002951.5	ENSP00000237530.6
MROH8	ENST00000343811.10	c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTCTATAAG		splice_acceptor_variant, splice_donor_variant, intron_variant	Intron 1 of 24	1		ENSP00000513568.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125068 AN: 151842 Hom.: 52316 Cov.: 0

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.796 AC: 1078807 AN: 1355542 Hom.: 431642 Cov.: 83 AF XY: 0.794 AC XY: 526884 AN XY: 663612

African (AFR) AF: 0.950 AC: 29338 AN: 30886

American (AMR) AF: 0.724 AC: 25120 AN: 34708

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 20688 AN: 24564

East Asian (EAS) AF: 0.587 AC: 20442 AN: 34832

South Asian (SAS) AF: 0.729 AC: 56601 AN: 77626

European-Finnish (FIN) AF: 0.694 AC: 24708 AN: 35584

Middle Eastern (MID) AF: 0.874 AC: 4343 AN: 4968

European-Non Finnish (NFE) AF: 0.807 AC: 852558 AN: 1056204

Other (OTH) AF: 0.801 AC: 45009 AN: 56170

GnomAD4 genome AF: 0.824 AC: 125160 AN: 151958 Hom.: 52352 Cov.: 0 AF XY: 0.816 AC XY: 60633 AN XY: 74266

African (AFR) AF: 0.940 AC: 38967 AN: 41462

American (AMR) AF: 0.802 AC: 12258 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2906 AN: 3466

East Asian (EAS) AF: 0.520 AC: 2672 AN: 5142

South Asian (SAS) AF: 0.726 AC: 3490 AN: 4804

European-Finnish (FIN) AF: 0.679 AC: 7162 AN: 10546

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 54991 AN: 67940

Other (OTH) AF: 0.837 AC: 1769 AN: 2114

Alfa AF: 0.812 Hom.: 4465

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66
Mutation Taster		=36/64	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11467214; hg19: chr20-35807790; COSMIC: COSV52903505; COSMIC: COSV52903505;