13-50843419-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001306135.2(DLEU7):c.228T>G(p.Ser76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000864 in 1,157,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 8.6e-7 (0 hom.)
• Consequence: DLEU7 NM_001306135.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.667

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051486462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLEU7	NM_001306135.2	c.228T>G	p.Ser76Arg	missense_variant	1/2	ENST00000504404.2
DLEU7-AS1	NR_046551.1	n.438+3325A>C		intron_variant, non_coding_transcript_variant
DLEU7	NM_198989.3	c.228T>G	p.Ser76Arg	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLEU7	ENST00000504404.2	c.228T>G	p.Ser76Arg	missense_variant	1/2	1	NM_001306135.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.64e-7 AC: 1 AN: 1157926 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 554572

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: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 11, 2021

The c.228T>G (p.S76R) alteration is located in exon 1 (coding exon 1) of the DLEU7 gene. This alteration results from a T to G substitution at nucleotide position 228, causing the serine (S) at amino acid position 76 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.47
Dann	Benign	0.80
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.022
Sift	Benign	0.063	T;T
Sift4G	Uncertain	0.037	D;T
Polyphen		0.0010	B;B
Vest4		0.17
MutPred		0.20		Loss of phosphorylation at S76 (P = 0.0036);Loss of phosphorylation at S76 (P = 0.0036);
MVP		0.072
MPC		0.93
ClinPred		0.076	T
GERP RS		-1.9
Varity_R		0.057
gMVP		0.037

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-51417555;