Genetic Variant DDX49:p.Pro177Gln (chr19-18922408-C-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_019070.5(DDX49):c.530C>A(p.Pro177Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P177R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DDX49
NM_019070.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.56

Publications

1 publications found

Variant links:

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]

DDX49 links:

ENSG00000268193 (HGNC:):

ENSG00000268193 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019070.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX49	NM_019070.5	MANE Select	c.530C>A	p.Pro177Gln	missense	Exon 5 of 13	NP_061943.2
	DDX49	NR_033677.2		n.486C>A		non_coding_transcript_exon	Exon 5 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDX49	ENST00000247003.9	TSL:1 MANE Select	c.530C>A	p.Pro177Gln	missense	Exon 5 of 13	ENSP00000247003.3	Q9Y6V7-1
DDX49	ENST00000595858.5	TSL:1	n.*105C>A		non_coding_transcript_exon	Exon 6 of 14	ENSP00000471292.1	M0R0K1
DDX49	ENST00000602113.5	TSL:1	n.*333C>A		non_coding_transcript_exon	Exon 5 of 13	ENSP00000469086.1	M0QXD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000418

AC:

AN:

239392

AF XY:

0.00000765

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000926

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457662

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

85854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111296

Other (OTH)

AF:

0.00

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.091

MetaRNN

Pathogenic

0.99

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.2

PhyloP100

7.6

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.91

MutPred

0.85

Loss of sheet (P = 0.1158)

MVP

0.62

MPC

1.1

ClinPred

0.95

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.70

gMVP

0.78

Mutation Taster

=63/37

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over