Variant rs3746429 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018217.3(EDEM2):c.1366G>A(p.Ala456Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,624 control chromosomes in the GnomAD database, including 22,198 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1517 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20681 hom. )

Consequence

EDEM2
NM_018217.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.560

Variant links:

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]

EDEM2 links:

MMP24-AS1-EDEM2 (HGNC:):

MMP24-AS1-EDEM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026990771).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
EDEM2	NM_018217.3 linkuse as main transcript	c.1366G>A	p.Ala456Thr	missense_variant	11/11	ENST00000374492.8	NP_060687.2
MMP24-AS1-EDEM2	NM_001355008.2 linkuse as main transcript	c.1243G>A	p.Ala415Thr	missense_variant	15/15		NP_001341937.1
EDEM2	NM_001145025.2 linkuse as main transcript	c.1255G>A	p.Ala419Thr	missense_variant	10/10		NP_001138497.1
EDEM2	NR_026728.2 linkuse as main transcript	n.1660G>A		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM2	ENST00000374492.8 linkuse as main transcript	c.1366G>A	p.Ala456Thr	missense_variant	11/11	1	NM_018217.3	ENSP00000363616	P1	Q9BV94-1
EDEM2	ENST00000374491.3 linkuse as main transcript	c.1255G>A	p.Ala419Thr	missense_variant	10/10	1		ENSP00000363615		Q9BV94-2

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19118

AN:

151676

Hom.:

1514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0279

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.0962

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.158

AC:

39580

AN:

251280

Hom.:

3512

AF XY:

0.166

AC XY:

22522

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0263

Gnomad AMR exome

AF:

0.0911

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.211

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.164

AC:

239956

AN:

1461832

Hom.:

20681

Cov.:

AF XY:

0.167

AC XY:

121425

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.0938

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.126

AC:

19122

AN:

151792

Hom.:

1517

Cov.:

AF XY:

0.127

AC XY:

9438

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.0277

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.0962

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.166

Hom.:

5457

Bravo

AF:

0.115

TwinsUK

AF:

0.167

AC:

620

ALSPAC

AF:

0.160

AC:

617

ESP6500AA

AF:

0.0338

AC:

149

ESP6500EA

AF:

0.177

AC:

1521

ExAC

AF:

0.159

AC:

19240

Asia WGS

AF:

0.177

AC:

617

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.9

DANN

Benign

0.78

DEOGEN2

Benign

0.069

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

N;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.0090

Sift

Benign

0.60

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0010

B;B

Vest4

0.033

MPC

0.33

ClinPred

0.00030

GERP RS

-0.27

Varity_R

0.017

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over