20-37236651-C-G

Variant names:

• chr20-37236651-C-G
• rs4608
• NM_002951.5:c.1825C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002951.5(RPN2):​c.1825C>G​(p.Leu609Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L609L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPN2 NM_002951.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 30 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28497428).

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.1825C>G	p.Leu609Val	missense	Exon 16 of 17	NP_002942.2
	RPN2	NM_001324301.2		c.1873C>G	p.Leu625Val	missense	Exon 17 of 19	NP_001311230.1
	RPN2	NM_001324304.2		c.1825C>G	p.Leu609Val	missense	Exon 16 of 18	NP_001311233.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPN2	ENST00000237530.11	TSL:1 MANE Select	c.1825C>G	p.Leu609Val	missense	Exon 16 of 17	ENSP00000237530.6	P04844-1
	RPN2	ENST00000705448.1		c.1825C>G	p.Leu609Val	missense	Exon 16 of 18	ENSP00000516126.1	A0A994J5J1
	RPN2	ENST00000892636.1		c.1894C>G	p.Leu632Val	missense	Exon 17 of 18	ENSP00000562695.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.40
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.067
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.055	T
Polyphen		0.48	P
Vest4		0.30
MutPred		0.52		Gain of methylation at K604 (P = 0.081)
MVP		0.54
MPC		0.23
ClinPred		0.30	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.49
Mutation Taster		=71/29	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: rs4608; hg19: chr20-35865054;