rs7994224

chr13-49978048-C-T

Variant summary

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

The ENST00000665220.1(DLEU2):n.1136G>A 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 0.174 in 152,174 control chromosomes in the GnomAD database, including 2,631 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 0.17 (2631 hom., cov: 31)
• Consequence: DLEU2 ENST00000665220.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914

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 (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEU2	ENST00000665220.1	n.1136G>A		non_coding_transcript_exon_variant	1/2
DLEU2	ENST00000651713.1	n.257-1594G>A		intron_variant, non_coding_transcript_variant
DLEU2	ENST00000658343.1	n.233-1594G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26443 AN: 152056 Hom.: 2625 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.174 AC: 26485 AN: 152174 Hom.: 2631 Cov.: 31 AF XY: 0.174 AC XY: 12922 AN XY: 74380

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.180

Alfa AF: 0.152 Hom.: 856

Bravo AF: 0.170

Asia WGS AF: 0.0920 AC: 320 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	1.0
Dann	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7994224; hg19: chr13-50552184;