dbSNP rs6120849: EDEM2:c.259-106G>A (chr20-35142584-C-T) – 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.259-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 758,902 control chromosomes in the GnomAD database, including 17,903 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 0.19 ( 3049 hom., cov: 32)

Exomes 𝑓: 0.21 ( 14854 hom. )

Consequence

EDEM2
NM_018217.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

51 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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
EDEM2	NM_018217.3 link	c.259-106G>A	intron_variant	Intron 3 of 10	ENST00000374492.8	NP_060687.2	Q9BV94-1
EDEM2	NM_001145025.2 link	c.148-106G>A	intron_variant	Intron 2 of 9		NP_001138497.1	Q9BV94-2
MMP24-AS1-EDEM2	NM_001355008.2 link	c.136-106G>A	intron_variant	Intron 7 of 14		NP_001341937.1
EDEM2	NR_026728.2 link	n.553-106G>A	intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDEM2	ENST00000374492.8 link	c.259-106G>A		intron_variant	Intron 3 of 10	1	NM_018217.3	ENSP00000363616.3		Q9BV94-1
EDEM2	ENST00000374491.3 link	c.148-106G>A		intron_variant	Intron 2 of 9	1		ENSP00000363615.2		Q9BV94-2

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29254

AN:

151860

Hom.:

3048

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.212

AC:

128644

AN:

606924

Hom.:

14854

AF XY:

0.215

AC XY:

68867

AN XY:

320902

show subpopulations

African (AFR)

AF:

0.144

AC:

2205

AN:

15328

American (AMR)

AF:

0.143

AC:

3164

AN:

22080

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

5080

AN:

16754

East Asian (EAS)

AF:

0.0338

AC:

1092

AN:

32328

South Asian (SAS)

AF:

0.246

AC:

13405

AN:

54542

European-Finnish (FIN)

AF:

0.257

AC:

9128

AN:

35546

Middle Eastern (MID)

AF:

0.334

AC:

1125

AN:

3364

European-Non Finnish (NFE)

AF:

0.219

AC:

86674

AN:

395350

Other (OTH)

AF:

0.214

AC:

6771

AN:

31632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

4911

9823

14734

19646

24557

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1252

2504

3756

5008

6260

<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:

0.193

AC:

29265

AN:

151978

Hom.:

3049

Cov.:

AF XY:

0.194

AC XY:

14399

AN XY:

74278

show subpopulations

African (AFR)

AF:

0.142

AC:

5907

AN:

41458

American (AMR)

AF:

0.165

AC:

2518

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1021

AN:

3466

East Asian (EAS)

AF:

0.0286

AC:

148

AN:

5176

South Asian (SAS)

AF:

0.253

AC:

1216

AN:

4810

European-Finnish (FIN)

AF:

0.258

AC:

2724

AN:

10544

Middle Eastern (MID)

AF:

0.332

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.220

AC:

14921

AN:

67946

Other (OTH)

AF:

0.215

AC:

453

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1177

2354

3532

4709

5886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.209

Hom.:

14095

Bravo

AF:

0.184

Asia WGS

AF:

0.192

AC:

668

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.93

(source)

DANN

Benign

0.36

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over