chr13-50050004-G-A

Position:

• chr13-50050004-G-A

Variant summary

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

The NR_152566.1(DLEU2):​n.577-342C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,924 control chromosomes in the GnomAD database, including 12,442 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 0.38 (12442 hom., cov: 32)
• Consequence: DLEU2 NR_152566.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLEU2	NR_152566.1	n.577-342C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEU2	ENST00000621282.4	n.577-342C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57533 AN: 151806 Hom.: 12447 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.379 AC: 57526 AN: 151924 Hom.: 12442 Cov.: 32 AF XY: 0.372 AC XY: 27612 AN XY: 74268

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.417

Alfa AF: 0.472 Hom.: 35358

Bravo AF: 0.369

Asia WGS AF: 0.225 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9535416; hg19: chr13-50624140;