NM_002951.5:c.14-109C>T

Variant names:

• chr20-37184071-C-T
• rs77007680
• NM_002951.5:c.14-109C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002951.5(RPN2):​c.14-109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 1,335,748 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (114 hom.)
• Consequence: RPN2 NM_002951.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0650
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-37184071-C-T is Benign according to our data. Variant chr20-37184071-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1318003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002951.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN2	NM_002951.5	MANE Select	c.14-109C>T		intron	N/A	NP_002942.2
	RPN2	NM_001324301.2		c.14-109C>T		intron	N/A	NP_001311230.1
	RPN2	NM_001324304.2		c.14-109C>T		intron	N/A	NP_001311233.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.14-109C>T		intron	N/A	ENSP00000237530.6	P04844-1
	RPN2	ENST00000705448.1		c.14-109C>T		intron	N/A	ENSP00000516126.1	A0A994J5J1
	RPN2	ENST00000892636.1		c.14-109C>T		intron	N/A	ENSP00000562695.1

Frequencies

GnomAD3 genomes AF: 0.00754 AC: 1147 AN: 152180 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0698

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.00564 AC: 6669 AN: 1183450 Hom.: 114 AF XY: 0.00572 AC XY: 3439 AN XY: 600762

African (AFR) AF: 0.000791 AC: 22 AN: 27822

American (AMR) AF: 0.0326 AC: 1422 AN: 43654

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 39 AN: 24252

East Asian (EAS) AF: 0.0567 AC: 2163 AN: 38178

South Asian (SAS) AF: 0.0104 AC: 830 AN: 79498

European-Finnish (FIN) AF: 0.0167 AC: 871 AN: 52008

Middle Eastern (MID) AF: 0.00387 AC: 20 AN: 5172

European-Non Finnish (NFE) AF: 0.000945 AC: 814 AN: 861666

Other (OTH) AF: 0.00953 AC: 488 AN: 51200

GnomAD4 genome AF: 0.00756 AC: 1152 AN: 152298 Hom.: 23 Cov.: 32 AF XY: 0.00929 AC XY: 692 AN XY: 74466

African (AFR) AF: 0.00152 AC: 63 AN: 41558

American (AMR) AF: 0.0212 AC: 324 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.0700 AC: 362 AN: 5172

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4826

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00128 AC: 87 AN: 68038

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00407 Hom.: 3

Bravo AF: 0.00803

Asia WGS AF: 0.0610 AC: 215 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.63
PhyloP100		-0.065
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs77007680; hg19: chr20-35812474;