2-74519699-C-T

Position:

• chr2-74519699-C-T

Variant summary

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

The NM_133637.3(DQX1):​c.1663G>A​(p.Ala555Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.80

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DQX1	NM_133637.3	c.1663G>A	p.Ala555Thr	missense_variant	10/12	ENST00000404568.4	NP_598376.2
DQX1	XM_047443583.1	c.1309G>A	p.Ala437Thr	missense_variant	9/11		XP_047299539.1
DQX1	XM_011532645.1	c.937G>A	p.Ala313Thr	missense_variant	7/9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4	c.1663G>A	p.Ala555Thr	missense_variant	10/12	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

Aug 30, 2022

The c.1663G>A (p.A555T) alteration is located in exon 10 (coding exon 9) of the DQX1 gene. This alteration results from a G to A substitution at nucleotide position 1663, causing the alanine (A) at amino acid position 555 to be replaced by a threonine (T). 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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	0.038
Eigen_PC	Benign	-0.00071
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.14
Sift	Benign	0.046	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.91	P;P
Vest4		0.56
MutPred		0.64		Loss of MoRF binding (P = 0.1739);Loss of MoRF binding (P = 0.1739);
MVP		0.29
MPC		0.38
ClinPred		0.99	D
GERP RS		2.7
Varity_R		0.13
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-74746826;