rs2295888

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDEM2	NM_018217.3	c.491-111T>C		intron_variant	Intron 5 of 10	ENST00000374492.8	NP_060687.2
EDEM2	NM_001145025.2	c.380-111T>C		intron_variant	Intron 4 of 9		NP_001138497.1
MMP24-AS1-EDEM2	NM_001355008.2	c.368-111T>C		intron_variant	Intron 9 of 14		NP_001341937.1
EDEM2	NR_026728.2	n.785-111T>C		intron_variant	Intron 4 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDEM2	ENST00000374492.8	c.491-111T>C		intron_variant	Intron 5 of 10	1	NM_018217.3	ENSP00000363616.3
EDEM2	ENST00000374491.3	c.380-111T>C		intron_variant	Intron 4 of 9	1		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

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.0494

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0567

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.0888

Gnomad4 OTH exome AF: 0.106

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

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0753

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.0942

Gnomad4 OTH AF: 0.114

Alfa AF: 0.102 Hom.: 1000

Bravo AF: 0.135

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.46

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

LitVar

Other links and lift over

dbSNP: rs2295888; hg19: chr20-33722863;