2-74519195-A-T

Variant names:

• chr2-74519195-A-T
• rs6546909
• NM_133637.3:c.1842T>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_133637.3(DQX1):​c.1842T>A​(p.Leu614Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,593,406 control chromosomes in the GnomAD database, including 56,858 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (14058 hom., cov: 32)
  • Exomes 𝑓: 0.19 (42800 hom.)
• Consequence: DQX1 NM_133637.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.192 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DQX1	NM_133637.3	c.1842T>A	p.Leu614Leu	synonymous_variant	Exon 11 of 12	ENST00000404568.4	NP_598376.2
DQX1	XM_047443583.1	c.1488T>A	p.Leu496Leu	synonymous_variant	Exon 10 of 11		XP_047299539.1
DQX1	XM_011532645.1	c.1116T>A	p.Leu372Leu	synonymous_variant	Exon 8 of 9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4	c.1842T>A	p.Leu614Leu	synonymous_variant	Exon 11 of 12	5	NM_133637.3	ENSP00000384621.3
DQX1	ENST00000393951.6	c.1842T>A	p.Leu614Leu	synonymous_variant	Exon 11 of 12	2		ENSP00000377523.2
DQX1	ENST00000418139.5	n.*662T>A		non_coding_transcript_exon_variant	Exon 8 of 9	5		ENSP00000389196.1
DQX1	ENST00000418139.5	n.*662T>A		3_prime_UTR_variant	Exon 8 of 9	5		ENSP00000389196.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52112 AN: 151944 Hom.: 14018 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.299

GnomAD2 exomes AF: 0.276 AC: 65148 AN: 236390 AF XY: 0.262

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.841

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.195 AC: 280944 AN: 1441344 Hom.: 42800 Cov.: 32 AF XY: 0.195 AC XY: 139755 AN XY: 715166

African (AFR) AF: 0.721 AC: 23463 AN: 32558

American (AMR) AF: 0.264 AC: 10794 AN: 40900

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4039 AN: 25420

East Asian (EAS) AF: 0.834 AC: 32793 AN: 39308

South Asian (SAS) AF: 0.294 AC: 24571 AN: 83540

European-Finnish (FIN) AF: 0.146 AC: 7729 AN: 53114

Middle Eastern (MID) AF: 0.192 AC: 1088 AN: 5668

European-Non Finnish (NFE) AF: 0.147 AC: 162318 AN: 1101406

Other (OTH) AF: 0.238 AC: 14149 AN: 59430

GnomAD4 genome AF: 0.343 AC: 52206 AN: 152062 Hom.: 14058 Cov.: 32 AF XY: 0.343 AC XY: 25464 AN XY: 74332

African (AFR) AF: 0.707 AC: 29297 AN: 41418

American (AMR) AF: 0.274 AC: 4182 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4234 AN: 5166

South Asian (SAS) AF: 0.321 AC: 1548 AN: 4818

European-Finnish (FIN) AF: 0.141 AC: 1497 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 10000 AN: 67998

Other (OTH) AF: 0.300 AC: 635 AN: 2116

Alfa AF: 0.187 Hom.: 1394

Bravo AF: 0.374

Asia WGS AF: 0.579 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.7
DANN	Benign	0.72
PhyloP100		-0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs6546909; hg19: chr2-74746322; COSMIC: COSV52045966; COSMIC: COSV52045966;