7-76482739-G-T

Position:

• chr7-76482739-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001102594.3(DTX2):​c.500G>T​(p.Ser167Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,626 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: 0.0000027 (0 hom.)
• Consequence: DTX2 NM_001102594.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40

Genes affected

DTX2 (HGNC:15973): (deltex E3 ubiquitin ligase 2) DTX2 functions as an E3 ubiquitin ligase (Takeyama et al., 2003 [PubMed 12670957]).[supplied by OMIM, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4233683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX2	NM_001102594.3	c.500G>T	p.Ser167Ile	missense_variant	4/11	ENST00000430490.7	NP_001096064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX2	ENST00000430490.7	c.500G>T	p.Ser167Ile	missense_variant	4/11	1	NM_001102594.3	ENSP00000411986.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461626 Hom.: 0 Cov.: 74 AF XY: 0.00000275 AC XY: 2 AN XY: 727122

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

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

Jan 22, 2024

The c.500G>T (p.S167I) alteration is located in exon 5 (coding exon 2) of the DTX2 gene. This alteration results from a G to T substitution at nucleotide position 500, causing the serine (S) at amino acid position 167 to be replaced by an isoleucine (I). 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	0.20
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;.;T;T;.
Eigen	Benign	0.013
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	.;T;.;T;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	L;.;L;L;L
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.015	D;D;D;D;D
Sift4G	Uncertain	0.024	D;D;D;D;D
Polyphen		0.86	P;.;P;P;P
Vest4		0.36
MutPred		0.53		Loss of disorder (P = 0.0058);.;Loss of disorder (P = 0.0058);Loss of disorder (P = 0.0058);Loss of disorder (P = 0.0058);
MVP		0.75
MPC		1.0
ClinPred		0.97	D
GERP RS		2.6
Varity_R		0.15
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-76112056; COSMIC: COSV56865183; COSMIC: COSV56865183;