20-37179387-G-GCTTACAGACAGGGCCCCGCGGCCGGCACT

Variant names:

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

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+22insACAGACAGGGCCCCGCGGCCGGCACTCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,507,316 control chromosomes in the GnomAD database, including 30,895 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 0.17 (2974 hom., cov: 0)
  • Exomes 𝑓: 0.19 (27921 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-GCTTACAGACAGGGCCCCGCGGCCGGCACT is Benign according to our data. Variant chr20-37179387-G-GCTTACAGACAGGGCCCCGCGGCCGGCACT is described in ClinVar as Likely_benign. ClinVar VariationId is 1148510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 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+22insACAGACAGGGCCCCGCGGCCGGCACTCTT		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+19insCTTACAGACAGGGCCCCGCGGCCGGCACT		intron_variant	Intron 1 of 16	1	NM_002951.5	ENSP00000237530.6
MROH8	ENST00000343811.10	c.92+1_93insAGTGCCGGCCGCGGGGCCCTGTCTGTAAG		splice_acceptor_variant, splice_donor_variant, intron_variant	Intron 1 of 24	1		ENSP00000513568.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25766 AN: 151848 Hom.: 2972 Cov.: 0

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.194 AC: 263244 AN: 1355352 Hom.: 27921 Cov.: 83 AF XY: 0.196 AC XY: 130220 AN XY: 663504

African (AFR) AF: 0.0481 AC: 1484 AN: 30878

American (AMR) AF: 0.272 AC: 9430 AN: 34674

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3569 AN: 24550

East Asian (EAS) AF: 0.413 AC: 14381 AN: 34818

South Asian (SAS) AF: 0.263 AC: 20447 AN: 77612

European-Finnish (FIN) AF: 0.289 AC: 10304 AN: 35612

Middle Eastern (MID) AF: 0.124 AC: 615 AN: 4968

European-Non Finnish (NFE) AF: 0.182 AC: 192358 AN: 1056076

Other (OTH) AF: 0.190 AC: 10656 AN: 56164

GnomAD4 genome AF: 0.170 AC: 25790 AN: 151964 Hom.: 2974 Cov.: 0 AF XY: 0.177 AC XY: 13148 AN XY: 74274

African (AFR) AF: 0.0581 AC: 2409 AN: 41458

American (AMR) AF: 0.195 AC: 2974 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2472 AN: 5148

South Asian (SAS) AF: 0.268 AC: 1288 AN: 4804

European-Finnish (FIN) AF: 0.306 AC: 3226 AN: 10540

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12319 AN: 67940

Other (OTH) AF: 0.158 AC: 334 AN: 2116

Alfa AF: 0.177 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 02, 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	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: COSV52903546; COSMIC: COSV52903546;