rs2476391

chr13-50044368-T-C

Variant summary

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

The ENST00000433070.8(DLEU2):n.778A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 152,066 control chromosomes in the GnomAD database, including 333 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 0.052 (333 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLEU2 ENST00000433070.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

Genes affected

DLEU2 (HGNC:13748): (deleted in lymphocytic leukemia 2) This locus represents a microRNA host gene and also produces long alternatively spliced non-coding RNAs. This genome region was observed to be deleted or epigenetically suppressed in leukemia, and was implicated as a negative regulator of cell proliferation. However, an alternative transcript produced at this locus was also found to promote progression through the cell cycle via angiotensin I converting enzyme 2 and cyclin D1. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLEU2	NR_152566.1	n.899+272A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEU2	ENST00000621282.4	n.899+272A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7956 AN: 151948 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0607

Gnomad OTH AF: 0.0670

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0523 AC: 7955 AN: 152066 Hom.: 333 Cov.: 32 AF XY: 0.0551 AC XY: 4093 AN XY: 74328

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.0590

Gnomad4 EAS AF: 0.0815

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.0664

Alfa AF: 0.0526 Hom.: 38

Bravo AF: 0.0485

Asia WGS AF: 0.135 AC: 461 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2476391; hg19: chr13-50618504;