NM_018217.3:c.1536G>T

Variant names:

• chr20-35115634-C-A
• NM_018217.3:c.1536G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018217.3(EDEM2):​c.1536G>T​(p.Arg512Ser) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EDEM2 NM_018217.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690
• Publications: 0 publications found

Genes affected

EDEM2 (HGNC:15877): (ER degradation enhancing alpha-mannosidase like protein 2) In the endoplasmic reticulum (ER), misfolded proteins are retrotranslocated to the cytosol and degraded by the proteasome in a process known as ER-associated degradation (ERAD). EDEM2 belongs to a family of proteins involved in ERAD of glycoproteins (Mast et al., 2005 [PubMed 15537790]).[supplied by OMIM, Mar 2008]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061107844).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018217.3. 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
	EDEM2	NM_018217.3	MANE Select	c.1536G>T	p.Arg512Ser	missense	Exon 11 of 11	NP_060687.2	Q9BV94-1
	EDEM2	NM_001145025.2		c.1425G>T	p.Arg475Ser	missense	Exon 10 of 10	NP_001138497.1	Q9BV94-2
	MMP24-AS1-EDEM2	NM_001355008.2		c.1413G>T	p.Arg471Ser	missense	Exon 15 of 15	NP_001341937.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM2	ENST00000374492.8	TSL:1 MANE Select	c.1536G>T	p.Arg512Ser	missense	Exon 11 of 11	ENSP00000363616.3	Q9BV94-1
	EDEM2	ENST00000374491.3	TSL:1	c.1425G>T	p.Arg475Ser	missense	Exon 10 of 10	ENSP00000363615.2	Q9BV94-2
	EDEM2	ENST00000881595.1		c.1584G>T	p.Arg528Ser	missense	Exon 12 of 12	ENSP00000551654.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	1.3
DANN	Benign	0.76
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.069
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.010
Sift	Benign	0.093	T
Sift4G	Benign	0.60	T
Polyphen		0.0030	B
Vest4		0.27
MutPred		0.31		Gain of phosphorylation at R512 (P = 0.0219)
MVP		0.19
MPC		0.38
ClinPred		0.020	T
GERP RS		-1.5
Varity_R		0.087
gMVP		0.47
Mutation Taster		=91/9	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

hg19: chr20-33703437;