rs6060266

Positions:

• chr20-35145275-T-C

Variant summary

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

The NM_018217.3(EDEM2):​c.219-257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,128 control chromosomes in the GnomAD database, including 3,924 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 0.22 (3924 hom., cov: 32)
• Consequence: EDEM2 NM_018217.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDEM2	NM_018217.3	c.219-257A>G		intron_variant		ENST00000374492.8	NP_060687.2
EDEM2	NM_001145025.2	c.108-257A>G		intron_variant			NP_001138497.1
MMP24-AS1-EDEM2	NM_001355008.2	c.96-257A>G		intron_variant			NP_001341937.1
EDEM2	NR_026728.2	n.513-257A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM2	ENST00000374492.8	c.219-257A>G		intron_variant		1	NM_018217.3	ENSP00000363616.3
EDEM2	ENST00000374491.3	c.108-257A>G		intron_variant		1		ENSP00000363615.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33768 AN: 152010 Hom.: 3920 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.232

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.222 AC: 33789 AN: 152128 Hom.: 3924 Cov.: 32 AF XY: 0.222 AC XY: 16508 AN XY: 74370

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.0289

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.236

Alfa AF: 0.225 Hom.: 495

Bravo AF: 0.218

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.87

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: rs6060266; hg19: chr20-33733078;