2-74518570-C-T

Position:

• chr2-74518570-C-T

Variant summary

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

The NM_133637.3(DQX1):​c.2030G>A​(p.Ser677Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 5.29

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]

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=0.15193802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DQX1	NM_133637.3	c.2030G>A	p.Ser677Asn	missense_variant	12/12	ENST00000404568.4	NP_598376.2
DQX1	XM_047443583.1	c.1676G>A	p.Ser559Asn	missense_variant	11/11		XP_047299539.1
DQX1	XM_011532645.1	c.1304G>A	p.Ser435Asn	missense_variant	9/9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4	c.2030G>A	p.Ser677Asn	missense_variant	12/12	5	NM_133637.3	ENSP00000384621.3
DQX1	ENST00000393951.6	c.2030G>A	p.Ser677Asn	missense_variant	12/12	2		ENSP00000377523.2
DQX1	ENST00000418139.5	n.*850G>A		non_coding_transcript_exon_variant	9/9	5		ENSP00000389196.1
DQX1	ENST00000418139.5	n.*850G>A		3_prime_UTR_variant	9/9	5		ENSP00000389196.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 02, 2024

The c.2030G>A (p.S677N) alteration is located in exon 12 (coding exon 11) of the DQX1 gene. This alteration results from a G to A substitution at nucleotide position 2030, causing the serine (S) at amino acid position 677 to be replaced by an asparagine (N). 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	0.22
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T
Eigen	Benign	-0.096
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.79	.;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.11
Sift	Benign	0.10	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.0	B;B
Vest4		0.32
MutPred		0.24		Loss of phosphorylation at S677 (P = 0.0554);Loss of phosphorylation at S677 (P = 0.0554);
MVP		0.23
MPC		0.29
ClinPred		0.91	D
GERP RS		4.1
Varity_R		0.15
gMVP		0.28

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: chr2-74745697;