2-74519677-A-C

Position:

• chr2-74519677-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_133637.3(DQX1):​c.1685T>G​(p.Leu562Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 8.83

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DQX1	NM_133637.3	c.1685T>G	p.Leu562Arg	missense_variant	10/12	ENST00000404568.4	NP_598376.2
DQX1	XM_047443583.1	c.1331T>G	p.Leu444Arg	missense_variant	9/11		XP_047299539.1
DQX1	XM_011532645.1	c.959T>G	p.Leu320Arg	missense_variant	7/9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4	c.1685T>G	p.Leu562Arg	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

May 15, 2024

The c.1685T>G (p.L562R) alteration is located in exon 10 (coding exon 9) of the DQX1 gene. This alteration results from a T to G substitution at nucleotide position 1685, causing the leucine (L) at amino acid position 562 to be replaced by an arginine (R). 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	0.18
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		1.0	D;D
Vest4		0.88
MutPred		0.78		Loss of catalytic residue at L562 (P = 0.0141);Loss of catalytic residue at L562 (P = 0.0141);
MVP		0.58
MPC		0.50
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.79
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-74746804;