dbSNP rs9750: DDX11:c.*694G>A (chr12-31104530-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030653.4(DDX11):c.*694G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 171,198 control chromosomes in the GnomAD database, including 25,988 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 0.54 ( 23458 hom., cov: 34)

Exomes 𝑓: 0.48 ( 2530 hom. )

Consequence

DDX11
NM_030653.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.199

Publications

17 publications found

Variant links:

Genes affected

DDX11 (HGNC:2736): (DEAD/H-box helicase 11) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

DDX11 Gene-Disease associations (from GenCC):

Warsaw breakage syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

DDX11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX11	NM_030653.4 link	c.*694G>A		3_prime_UTR_variant	Exon 27 of 27	ENST00000542838.6	NP_085911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX11	ENST00000542838.6 link	c.*694G>A		3_prime_UTR_variant	Exon 27 of 27	1	NM_030653.4	ENSP00000443426.1

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82252

AN:

151970

Hom.:

23403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.457

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.388

Gnomad EAS

AF:

0.817

Gnomad SAS

AF:

0.571

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.526

GnomAD4 exome

AF:

0.483

AC:

9222

AN:

19110

Hom.:

2530

Cov.:

AF XY:

0.489

AC XY:

4833

AN XY:

9884

show subpopulations

African (AFR)

AF:

0.606

AC:

240

AN:

396

American (AMR)

AF:

0.611

AC:

1963

AN:

3214

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

AN:

258

East Asian (EAS)

AF:

0.815

AC:

1110

AN:

1362

South Asian (SAS)

AF:

0.525

AC:

1102

AN:

2100

European-Finnish (FIN)

AF:

0.323

AC:

117

AN:

362

Middle Eastern (MID)

AF:

0.395

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

4193

AN:

10492

Other (OTH)

AF:

0.444

AC:

394

AN:

888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

197

394

592

789

986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.542

AC:

82361

AN:

152088

Hom.:

23458

Cov.:

AF XY:

0.544

AC XY:

40434

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.679

AC:

28186

AN:

41508

American (AMR)

AF:

0.598

AC:

9145

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.388

AC:

1345

AN:

3468

East Asian (EAS)

AF:

0.818

AC:

4222

AN:

5164

South Asian (SAS)

AF:

0.570

AC:

2748

AN:

4818

European-Finnish (FIN)

AF:

0.425

AC:

4491

AN:

10578

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30570

AN:

67948

Other (OTH)

AF:

0.525

AC:

1108

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1840

3680

5519

7359

9199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.495

Hom.:

2428

Bravo

AF:

0.564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.1

(source)

DANN

Benign

0.69

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over