rs3746429

Variant names:

• chr20-35115804-C-A
• NM_018217.3:c.1366G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-35115804-C-A
• chr20-35115804-C-G
• chr20-35115804-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A456T) has been classified as Likely benign.

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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034143478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDEM2	NM_018217.3	c.1366G>T	p.Ala456Ser	missense_variant	Exon 11 of 11	ENST00000374492.8	NP_060687.2
EDEM2	NM_001145025.2	c.1255G>T	p.Ala419Ser	missense_variant	Exon 10 of 10		NP_001138497.1
MMP24-AS1-EDEM2	NM_001355008.2	c.1243G>T	p.Ala415Ser	missense_variant	Exon 15 of 15		NP_001341937.1
EDEM2	NR_026728.2	n.1660G>T		non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDEM2	ENST00000374492.8	c.1366G>T	p.Ala456Ser	missense_variant	Exon 11 of 11	1	NM_018217.3	ENSP00000363616.3
EDEM2	ENST00000374491.3	c.1255G>T	p.Ala419Ser	missense_variant	Exon 10 of 10	1		ENSP00000363615.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.29	N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.0090
Sift	Benign	0.63	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	B;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33703607;