rs765903594

Variant names:

• chr7-76480525-A-G
• rs765903594
• NM_001102594.3:c.16A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001102594.3(DTX2):​c.16A>G​(p.Ser6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,453,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: DTX2 NM_001102594.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.355
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045098394).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102594.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTX2	NM_001102594.3	MANE Select	c.16A>G	p.Ser6Gly	missense	Exon 3 of 11	NP_001096064.1	Q86UW9-1
	DTX2	NM_001102595.3		c.16A>G	p.Ser6Gly	missense	Exon 2 of 10	NP_001096065.1	Q86UW9-1
	DTX2	NM_020892.4		c.16A>G	p.Ser6Gly	missense	Exon 4 of 12	NP_065943.2	Q86UW9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTX2	ENST00000430490.7	TSL:1 MANE Select	c.16A>G	p.Ser6Gly	missense	Exon 3 of 11	ENSP00000411986.2	Q86UW9-1
	DTX2	ENST00000324432.9	TSL:1	c.16A>G	p.Ser6Gly	missense	Exon 4 of 12	ENSP00000322885.5	Q86UW9-1
	DTX2	ENST00000413936.6	TSL:1	c.16A>G	p.Ser6Gly	missense	Exon 2 of 10	ENSP00000390218.2	Q86UW9-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 242752 AF XY: 0.00000758

Gnomad AFR exome AF: 0.0000641

Gnomad AMR exome AF: 0.0000892

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000551 AC: 8 AN: 1453050 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722142

African (AFR) AF: 0.0000901 AC: 3 AN: 33292

American (AMR) AF: 0.0000907 AC: 4 AN: 44082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25688

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4220

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107900

Other (OTH) AF: 0.00 AC: 0 AN: 59878

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.1
DANN	Benign	0.70
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.35
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.038
Sift	Benign	0.25	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.21		Loss of glycosylation at S6 (P = 0.0057)
MVP		0.37
MPC		0.25
ClinPred		0.11	T
GERP RS		-5.8
PromoterAI		0.035	Neutral
Varity_R		0.080
gMVP		0.38
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs765903594; hg19: chr7-76109842;