chr20-35115804-C-A

Variant names:

• chr20-35115804-C-A
• rs3746429
• NM_018217.3:c.1366G>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.1366G>T​(p.Ala456Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EDEM2 NM_018217.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• 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=0.034143478).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM2	NM_018217.3	MANE Select	c.1366G>T	p.Ala456Ser	missense	Exon 11 of 11	NP_060687.2
	EDEM2	NM_001145025.2		c.1255G>T	p.Ala419Ser	missense	Exon 10 of 10	NP_001138497.1
	MMP24-AS1-EDEM2	NM_001355008.2		c.1243G>T	p.Ala415Ser	missense	Exon 15 of 15	NP_001341937.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM2	ENST00000374492.8	TSL:1 MANE Select	c.1366G>T	p.Ala456Ser	missense	Exon 11 of 11	ENSP00000363616.3
	EDEM2	ENST00000374491.3	TSL:1	c.1255G>T	p.Ala419Ser	missense	Exon 10 of 10	ENSP00000363615.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.1
DANN	Benign	0.70
DEOGEN2	Benign	0.077	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.29	N
PhyloP100		0.56
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.0090
Sift	Benign	0.63	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.36		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.15
MPC		0.31
ClinPred		0.027	T
GERP RS		-0.27
Varity_R		0.024
gMVP		0.31
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3746429; hg19: chr20-33703607;