rs374430695

Variant names:

• chr17-5481389-T-C
• rs374430695
• NM_016041.5:c.234A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_016041.5(DERL2):​c.234A>G​(p.Leu78Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000571 in 1,610,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: DERL2 NM_016041.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.0007167
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.38
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 17-5481389-T-C is Benign according to our data. Variant chr17-5481389-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3501181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.38 with no splicing effect.
• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016041.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DERL2	NM_016041.5	MANE Select	c.234A>G	p.Leu78Leu	splice_region synonymous	Exon 4 of 7	NP_057125.2
	DERL2	NM_001304777.2		c.231A>G	p.Leu77Leu	splice_region synonymous	Exon 4 of 7	NP_001291706.1
	DERL2	NM_001304779.2		c.160-1245A>G		intron	N/A	NP_001291708.1	I3L3R8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DERL2	ENST00000158771.9	TSL:1 MANE Select	c.234A>G	p.Leu78Leu	splice_region synonymous	Exon 4 of 7	ENSP00000158771.4	Q9GZP9
	DERL2	ENST00000889580.1		c.234A>G	p.Leu78Leu	splice_region synonymous	Exon 4 of 8	ENSP00000559639.1
	DERL2	ENST00000889592.1		c.231A>G	p.Leu77Leu	splice_region synonymous	Exon 4 of 8	ENSP00000559651.1

Frequencies

GnomAD3 genomes AF: 0.0000722 AC: 11 AN: 152262 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000479 AC: 12 AN: 250574 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000555 AC: 81 AN: 1458516 Hom.: 0 Cov.: 29 AF XY: 0.0000565 AC XY: 41 AN XY: 725876

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000721 AC: 80 AN: 1109236

Other (OTH) AF: 0.0000166 AC: 1 AN: 60286

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74386

African (AFR) AF: 0.0000965 AC: 4 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.0000642

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.81
PhyloP100		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00072
dbscSNV1_RF	Benign	0.22
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: rs374430695; hg19: chr17-5384709;