rs2295888

Variant names:

• chr20-35135060-A-G
• rs2295888
• NM_018217.3:c.491-111T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 31 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: 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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20730 AN: 150282 Hom.: 1744 Cov.: 31

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

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

GnomAD4 genome AF: 0.138 AC: 20776 AN: 150402 Hom.: 1757 Cov.: 31 AF XY: 0.141 AC XY: 10377 AN XY: 73376

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: 26 AN: 290

European-Non Finnish (NFE) AF: 0.0942 AC: 6366 AN: 67590

Other (OTH) AF: 0.114 AC: 236 AN: 2078

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
DANN	Benign	0.46
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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: rs2295888; hg19: chr20-33722863;