7-76480729-C-A

Variant names:

• chr7-76480729-C-A
• rs1428371798
• NM_001102594.3:c.220C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001102594.3(DTX2):​c.220C>A​(p.Pro74Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,460,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: DTX2 NM_001102594.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 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.220C>A	p.Pro74Thr	missense	Exon 3 of 11	NP_001096064.1	Q86UW9-1
	DTX2	NM_001102595.3		c.220C>A	p.Pro74Thr	missense	Exon 2 of 10	NP_001096065.1	Q86UW9-1
	DTX2	NM_020892.4		c.220C>A	p.Pro74Thr	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.220C>A	p.Pro74Thr	missense	Exon 3 of 11	ENSP00000411986.2	Q86UW9-1
	DTX2	ENST00000324432.9	TSL:1	c.220C>A	p.Pro74Thr	missense	Exon 4 of 12	ENSP00000322885.5	Q86UW9-1
	DTX2	ENST00000413936.6	TSL:1	c.220C>A	p.Pro74Thr	missense	Exon 2 of 10	ENSP00000390218.2	Q86UW9-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460848 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726700

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111504

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 31

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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.31
Sift	Benign	0.094	T
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.59		Loss of loop (P = 0.0804)
MVP		0.84
MPC		1.0
ClinPred		0.98	D
GERP RS		5.7
PromoterAI		-0.00040	Neutral
Varity_R		0.52
gMVP		0.45
Mutation Taster		=59/41	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: rs1428371798; hg19: chr7-76110046;