13-50843642-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001306135.2(DLEU7):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,355,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: DLEU7 NM_001306135.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.503

Genes affected

DLEU7 (HGNC:17567): (deleted in lymphocytic leukemia 7)

DLEU1 (HGNC:13747): (deleted in lymphocytic leukemia 1)

DLEU7-AS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2575028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLEU7	NM_001306135.2	c.5C>T	p.Ala2Val	missense_variant	1/2	ENST00000504404.2
DLEU7-AS1	NR_046551.1	n.438+3548G>A		intron_variant, non_coding_transcript_variant
DLEU7	NM_198989.3	c.5C>T	p.Ala2Val	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEU7	ENST00000504404.2	c.5C>T	p.Ala2Val	missense_variant	1/2	1	NM_001306135.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000516 AC: 7 AN: 1355774 Hom.: 0 Cov.: 32 AF XY: 0.00000598 AC XY: 4 AN XY: 669200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000656

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the DLEU7 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	19
Dann	Uncertain	1.0
Eigen	Benign	-0.043
Eigen_PC	Benign	-0.084
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.11
Sift	Uncertain	0.013	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.70	P;P
Vest4		0.22
MutPred		0.20		Loss of glycosylation at P4 (P = 0.064);Loss of glycosylation at P4 (P = 0.064);
MVP		0.34
MPC		1.3
ClinPred		0.90	D
GERP RS		2.2
Varity_R		0.15
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs1220314912; hg19: chr13-51417778;