rs7994224

Variant names:

• chr13-49978048-C-T
• rs7994224
• ENST00000665220.2:n.1136G>A

Variant summary

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

The ENST00000665220.2(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 ENST00000665220.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLEU2	ENST00000665220.2	n.1136G>A		non_coding_transcript_exon_variant	Exon 1 of 2
DLEU2	ENST00000651713.2	n.1049-1594G>A		intron_variant	Intron 5 of 6
DLEU2	ENST00000658343.1	n.233-1594G>A		intron_variant	Intron 2 of 2

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

African (AFR) AF: 0.257 AC: 10679 AN: 41502

American (AMR) AF: 0.122 AC: 1867 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3468

East Asian (EAS) AF: 0.0322 AC: 167 AN: 5180

South Asian (SAS) AF: 0.135 AC: 650 AN: 4826

European-Finnish (FIN) AF: 0.201 AC: 2125 AN: 10576

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9763 AN: 68016

Other (OTH) AF: 0.180 AC: 380 AN: 2114

Alfa AF: 0.153 Hom.: 976

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
PhyloP100		-0.91

Splicing

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

Other links and lift over

dbSNP: rs7994224; hg19: chr13-50552184;