Genetic Variant DDX6:c.*8-179A>G (chr11-118752276-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004397.6(DDX6):c.*8-179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,068 control chromosomes in the GnomAD database, including 3,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 3959 hom., cov: 31)

Consequence

DDX6
NM_004397.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

Publications

8 publications found

Variant links:

Genes affected

DDX6 (HGNC:2747): (DEAD-box helicase 6) This gene encodes a member of the DEAD box protein family. The protein is an RNA helicase found in P-bodies and stress granules, and functions in translation suppression and mRNA degradation. It is required for microRNA-induced gene silencing. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Mar 2012]

DDX6 Gene-Disease associations (from GenCC):

intellectual developmental disorder with impaired language and dysmorphic facies
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DDX6 links:

ENSG00000308658 (HGNC:):

ENSG00000308658 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 11-118752276-T-C is Benign according to our data. Variant chr11-118752276-T-C is described in ClinVar as Benign. ClinVar VariationId is 1300447.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004397.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDX6	NM_004397.6	MANE Select	c.*8-179A>G	intron	N/A	NP_004388.2	P26196
DDX6	NM_001257191.3		c.*8-179A>G	intron	N/A	NP_001244120.1	P26196
DDX6	NM_001425145.1		c.*8-179A>G	intron	N/A	NP_001412074.1	P26196

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDX6	ENST00000534980.7	TSL:1 MANE Select	c.*8-179A>G	intron	N/A	ENSP00000442266.1	P26196
DDX6	ENST00000620157.4	TSL:1	c.*8-179A>G	intron	N/A	ENSP00000478754.1	P26196
DDX6	ENST00000953098.1		c.*8-179A>G	intron	N/A	ENSP00000623157.1

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34143

AN:

151946

Hom.:

3957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.327

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.225

AC:

34154

AN:

152068

Hom.:

3959

Cov.:

AF XY:

0.225

AC XY:

16701

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.181

AC:

7504

AN:

41506

American (AMR)

AF:

0.179

AC:

2737

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

902

AN:

3464

East Asian (EAS)

AF:

0.289

AC:

1497

AN:

5172

South Asian (SAS)

AF:

0.326

AC:

1570

AN:

4814

European-Finnish (FIN)

AF:

0.254

AC:

2681

AN:

10556

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16436

AN:

67972

Other (OTH)

AF:

0.246

AC:

519

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1343

2686

4029

5372

6715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.226

Hom.:

730

Bravo

AF:

0.216

Asia WGS

AF:

0.311

AC:

1084

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.19

(source)

DANN

Benign

0.19

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over