2-74520025-C-A

Position:

• chr2-74520025-C-A

Variant summary

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

The NM_133637.3(DQX1):​c.1505G>T​(p.Gly502Val) 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. 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)
• Consequence: DQX1 NM_133637.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

Genes affected

DQX1 (HGNC:20410): (DEAQ-box RNA dependent ATPase 1) Predicted to enable RNA binding activity. Predicted to be involved in DNA duplex unwinding. Predicted to be part of spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

DQX1 (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=0.19084242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DQX1	NM_133637.3	c.1505G>T	p.Gly502Val	missense_variant	9/12	ENST00000404568.4	NP_598376.2
DQX1	XM_047443583.1	c.1151G>T	p.Gly384Val	missense_variant	8/11		XP_047299539.1
DQX1	XM_011532645.1	c.779G>T	p.Gly260Val	missense_variant	6/9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4	c.1505G>T	p.Gly502Val	missense_variant	9/12	5	NM_133637.3	ENSP00000384621.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Dec 07, 2023

The c.1505G>T (p.G502V) alteration is located in exon 9 (coding exon 8) of the DQX1 gene. This alteration results from a G to T substitution at nucleotide position 1505, causing the glycine (G) at amino acid position 502 to be replaced by a valine (V). 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	0.096
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0063	T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-3.1	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.92	N;N
REVEL	Benign	0.16
Sift	Benign	0.073	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.16	B;B
Vest4		0.45
MutPred		0.33		Loss of disorder (P = 0.0405);Loss of disorder (P = 0.0405);
MVP		0.23
MPC		0.55
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr2-74747152;