7-76480612-A-G

Position:

• chr7-76480612-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001102594.3(DTX2):​c.103A>G​(p.Ser35Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: DTX2 NM_001102594.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.52

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTX2	NM_001102594.3	c.103A>G	p.Ser35Gly	missense_variant	3/11	ENST00000430490.7	NP_001096064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTX2	ENST00000430490.7	c.103A>G	p.Ser35Gly	missense_variant	3/11	1	NM_001102594.3	ENSP00000411986.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461130 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726874

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: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000166

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

Jul 27, 2022

The c.103A>G (p.S35G) alteration is located in exon 4 (coding exon 1) of the DTX2 gene. This alteration results from a A to G substitution at nucleotide position 103, causing the serine (S) at amino acid position 35 to be replaced by a glycine (G). 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	0.070
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	.;T;.;T;T;T;T;T;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D;.;T;.;T;.;D;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	.;M;.;M;.;.;M;.;.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.3	D;N;D;N;D;D;N;D;D;D
REVEL	Benign	0.23
Sift	Benign	0.036	D;T;D;T;D;D;T;D;D;D
Sift4G	Pathogenic	0.0	D;T;D;T;T;D;T;T;D;T
Polyphen		0.99, 0.91	.;D;.;D;.;.;D;.;.;P
Vest4		0.42, 0.42, 0.42, 0.45
MutPred		0.73		Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);Loss of stability (P = 0.0369);
MVP		0.85
MPC		0.92
ClinPred		0.95	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs1809072208; hg19: chr7-76109929;