rs6120849

Positions:

• chr20-35142584-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDEM2	NM_018217.3	c.259-106G>A		intron_variant		ENST00000374492.8	NP_060687.2
EDEM2	NM_001145025.2	c.148-106G>A		intron_variant			NP_001138497.1
MMP24-AS1-EDEM2	NM_001355008.2	c.136-106G>A		intron_variant			NP_001341937.1
EDEM2	NR_026728.2	n.553-106G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM2	ENST00000374492.8	c.259-106G>A		intron_variant		1	NM_018217.3	ENSP00000363616.3
EDEM2	ENST00000374491.3	c.148-106G>A		intron_variant		1		ENSP00000363615.2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29254 AN: 151860 Hom.: 3048 Cov.: 32

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

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.0338

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.257

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.193 AC: 29265 AN: 151978 Hom.: 3049 Cov.: 32 AF XY: 0.194 AC XY: 14399 AN XY: 74278

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.0286

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.215

Alfa AF: 0.215 Hom.: 7009

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
DANN	Benign	0.36

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

LitVar

Other links and lift over

dbSNP: rs6120849; hg19: chr20-33730387;