17-5478711-C-T

Variant names:

• chr17-5478711-C-T
• rs3865351
• NM_016041.5:c.614+1343G>A

Variant summary

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

The NM_016041.5(DERL2):​c.614+1343G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,104 control chromosomes in the GnomAD database, including 16,747 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 0.43 (16747 hom., cov: 33)
• Consequence: DERL2 NM_016041.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 11 publications found

Genes affected

DERL2 (HGNC:17943): (derlin 2) Proteins that are unfolded or misfolded in the endoplasmic reticulum (ER) must be refolded or degraded to maintain the homeostasis of the ER. DERL2 is involved in the degradation of misfolded glycoproteins in the ER (Oda et al., 2006 [PubMed 16449189]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DERL2	NM_016041.5	c.614+1343G>A		intron_variant	Intron 6 of 6	ENST00000158771.9	NP_057125.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DERL2	ENST00000158771.9	c.614+1343G>A		intron_variant	Intron 6 of 6	1	NM_016041.5	ENSP00000158771.4

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65492 AN: 151984 Hom.: 16683 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.431 AC: 65617 AN: 152104 Hom.: 16747 Cov.: 33 AF XY: 0.429 AC XY: 31892 AN XY: 74344

African (AFR) AF: 0.720 AC: 29868 AN: 41492

American (AMR) AF: 0.284 AC: 4338 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1775 AN: 5176

South Asian (SAS) AF: 0.380 AC: 1833 AN: 4822

European-Finnish (FIN) AF: 0.363 AC: 3834 AN: 10548

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21536 AN: 67986

Other (OTH) AF: 0.398 AC: 842 AN: 2114

Alfa AF: 0.345 Hom.: 7546

Bravo AF: 0.439

Asia WGS AF: 0.416 AC: 1450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.70
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3865351; hg19: chr17-5382031; COSMIC: COSV50147162; COSMIC: COSV50147162;