7-76482639-C-G

Position:

• chr7-76482639-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001102594.3(DTX2):​c.400C>G​(p.Gln134Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DTX2 NM_001102594.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.05

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]

DTX2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23790327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX2	NM_001102594.3	c.400C>G	p.Gln134Glu	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.400C>G	p.Gln134Glu	missense_variant	4/11	1	NM_001102594.3	ENSP00000411986.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 40

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

Oct 24, 2024

The c.400C>G (p.Q134E) alteration is located in exon 5 (coding exon 2) of the DTX2 gene. This alteration results from a C to G substitution at nucleotide position 400, causing the glutamine (Q) at amino acid position 134 to be replaced by a glutamic acid (E). 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	0.087
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.085	T;.;T;T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	0.011
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	.;T;.;T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.;L;.;L;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.60	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.34	T;T;T;T;T;T
Sift4G	Benign	0.99	T;T;T;T;T;T
Polyphen		0.055	B;.;B;.;B;B
Vest4		0.23
MutPred		0.47		Gain of phosphorylation at Y131 (P = 0.2327);.;Gain of phosphorylation at Y131 (P = 0.2327);Gain of phosphorylation at Y131 (P = 0.2327);Gain of phosphorylation at Y131 (P = 0.2327);Gain of phosphorylation at Y131 (P = 0.2327);
MVP		0.67
MPC		1.0
ClinPred		0.52	D
GERP RS		5.4
Varity_R		0.11
gMVP		0.65

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: chr7-76111956;