rs2301659

Variant names:

• chr19-18924545-G-T
• rs2301659
• NM_019070.5:c.853-78G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019070.5(DDX49):​c.853-78G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,498,574 control chromosomes in the GnomAD database, including 148,948 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 0.37 (12319 hom., cov: 32)
  • Exomes 𝑓: 0.44 (136629 hom.)
• Consequence: DDX49 NM_019070.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 7 publications found

Genes affected

DDX49 (HGNC:18684): (DEAD-box helicase 49) Enables RNA binding activity. Involved in positive regulation of cell growth and regulation of rRNA stability. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268193 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX49	NM_019070.5	c.853-78G>T		intron_variant	Intron 7 of 12	ENST00000247003.9	NP_061943.2
DDX49	NR_033677.2	n.809-78G>T		intron_variant	Intron 7 of 12
DDX49	XM_011528084.4	c.532-78G>T		intron_variant	Intron 8 of 13		XP_011526386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX49	ENST00000247003.9	c.853-78G>T		intron_variant	Intron 7 of 12	1	NM_019070.5	ENSP00000247003.3
ENSG00000268193	ENST00000596918.5	n.*167+6780C>A		intron_variant	Intron 4 of 6	5		ENSP00000469669.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55955 AN: 151752 Hom.: 12313 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.590

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.443 AC: 596386 AN: 1346704 Hom.: 136629 AF XY: 0.440 AC XY: 297505 AN XY: 675984

African (AFR) AF: 0.120 AC: 3654 AN: 30576

American (AMR) AF: 0.567 AC: 25062 AN: 44172

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 15460 AN: 25362

East Asian (EAS) AF: 0.296 AC: 11575 AN: 39104

South Asian (SAS) AF: 0.296 AC: 24789 AN: 83694

European-Finnish (FIN) AF: 0.424 AC: 22162 AN: 52222

Middle Eastern (MID) AF: 0.563 AC: 3135 AN: 5570

European-Non Finnish (NFE) AF: 0.462 AC: 466386 AN: 1009354

Other (OTH) AF: 0.427 AC: 24163 AN: 56650

GnomAD4 genome AF: 0.369 AC: 55965 AN: 151870 Hom.: 12319 Cov.: 32 AF XY: 0.369 AC XY: 27370 AN XY: 74188

African (AFR) AF: 0.127 AC: 5260 AN: 41482

American (AMR) AF: 0.533 AC: 8136 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2091 AN: 3468

East Asian (EAS) AF: 0.286 AC: 1471 AN: 5152

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4812

European-Finnish (FIN) AF: 0.424 AC: 4448 AN: 10490

Middle Eastern (MID) AF: 0.579 AC: 168 AN: 290

European-Non Finnish (NFE) AF: 0.465 AC: 31596 AN: 67900

Other (OTH) AF: 0.433 AC: 916 AN: 2114

Alfa AF: 0.427 Hom.: 3039

Bravo AF: 0.372

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs2301659; hg19: chr19-19035354; COSMIC: COSV55358658; COSMIC: COSV55358658;