Genetic Variant NM_018217.3:c.491-111T>C (chr20-35135060-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018217.3(EDEM2):c.491-111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,066,662 control chromosomes in the GnomAD database, including 7,184 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1757 hom., cov: 31)

Exomes 𝑓: 0.099 ( 5427 hom. )

Consequence

EDEM2
NM_018217.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.513

Publications

31 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDEM2	NM_018217.3	MANE Select	c.491-111T>C	intron	N/A	NP_060687.2	Q9BV94-1
EDEM2	NM_001145025.2		c.380-111T>C	intron	N/A	NP_001138497.1	Q9BV94-2
MMP24-AS1-EDEM2	NM_001355008.2		c.368-111T>C	intron	N/A	NP_001341937.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDEM2	ENST00000374492.8	TSL:1 MANE Select	c.491-111T>C	intron	N/A	ENSP00000363616.3	Q9BV94-1
EDEM2	ENST00000374491.3	TSL:1	c.380-111T>C	intron	N/A	ENSP00000363615.2	Q9BV94-2
EDEM2	ENST00000881595.1		c.491-111T>C	intron	N/A	ENSP00000551654.1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20730

AN:

150282

Hom.:

1744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.0863

Gnomad AMR

AF:

0.0849

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.0759

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0968

Gnomad NFE

AF:

0.0942

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.0990

AC:

90752

AN:

916260

Hom.:

5427

AF XY:

0.102

AC XY:

47476

AN XY:

466144

show subpopulations

African (AFR)

AF:

0.237

AC:

5443

AN:

22924

American (AMR)

AF:

0.0494

AC:

1658

AN:

33562

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

2308

AN:

19522

East Asian (EAS)

AF:

0.0567

AC:

2013

AN:

35504

South Asian (SAS)

AF:

0.175

AC:

11304

AN:

64666

European-Finnish (FIN)

AF:

0.132

AC:

4570

AN:

34638

Middle Eastern (MID)

AF:

0.120

AC:

415

AN:

3470

European-Non Finnish (NFE)

AF:

0.0888

AC:

58564

AN:

659748

Other (OTH)

AF:

0.106

AC:

4477

AN:

42226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

4119

8238

12358

16477

20596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1740

3480

5220

6960

8700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.138

AC:

20776

AN:

150402

Hom.:

1757

Cov.:

AF XY:

0.141

AC XY:

10377

AN XY:

73376

show subpopulations

African (AFR)

AF:

0.239

AC:

9839

AN:

41200

American (AMR)

AF:

0.0846

AC:

1247

AN:

14746

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

441

AN:

3460

East Asian (EAS)

AF:

0.0753

AC:

375

AN:

4982

South Asian (SAS)

AF:

0.160

AC:

757

AN:

4742

European-Finnish (FIN)

AF:

0.135

AC:

1412

AN:

10422

Middle Eastern (MID)

AF:

0.0897

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0942

AC:

6366

AN:

67590

Other (OTH)

AF:

0.114

AC:

236

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

861

1722

2583

3444

4305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.109

Hom.:

3442

Bravo

AF:

0.135

Asia WGS

AF:

0.137

AC:

477

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.5

(source)

DANN

Benign

0.46

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over