Variant 13-50843558-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001306135.2(DLEU7):c.89G>T(p.Trp30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,482,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

DLEU7
NM_001306135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0590

Variant links:

Genes affected

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

DLEU7 links:

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

DLEU1 links:

DLEU7-AS1 (HGNC:):

DLEU7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10749793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DLEU7	NM_001306135.2 linkuse as main transcript	c.89G>T	p.Trp30Leu	missense_variant	1/2	ENST00000504404.2
DLEU7-AS1	NR_046551.1 linkuse as main transcript	n.438+3464C>A		intron_variant, non_coding_transcript_variant
DLEU7	NM_198989.3 linkuse as main transcript	c.89G>T	p.Trp30Leu	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEU7	ENST00000504404.2 linkuse as main transcript	c.89G>T	p.Trp30Leu	missense_variant	1/2	1	NM_001306135.2	P1	Q6UYE1-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000252

AC:

AN:

79318

Hom.:

AF XY:

0.0000218

AC XY:

AN XY:

45826

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000341

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.0000504

AC:

AN:

1330676

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

656196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000397

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000541

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000586

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.89G>T (p.W30L) alteration is located in exon 1 (coding exon 1) of the DLEU7 gene. This alteration results from a G to T substitution at nucleotide position 89, causing the tryptophan (W) at amino acid position 30 to be replaced by a leucine (L). 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

0.22

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Benign

0.92

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.95

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Benign

0.065

Sift

Benign

0.39

T;T

Sift4G

Benign

0.066

T;T

Polyphen

0.56

P;B

Vest4

0.31

MutPred

0.48

Gain of disorder (P = 0.0365);Gain of disorder (P = 0.0365);

MVP

0.29

MPC

1.4

ClinPred

0.20

GERP RS

1.4

Varity_R

0.20

gMVP

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over