Genetic Variant DDX6:c.1175-4delT (chr11-118755506-TA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_004397.6(DDX6):c.1175-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,160,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.019 ( 0 hom. )

Consequence

DDX6
NM_004397.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 49 AD gene.

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.1175-4delT	splice_region intron	N/A	NP_004388.2	P26196
DDX6	NM_001257191.3		c.1175-4delT	splice_region intron	N/A	NP_001244120.1	P26196
DDX6	NM_001425145.1		c.1175-4delT	splice_region 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.1175-4delT	splice_region intron	N/A	ENSP00000442266.1	P26196
DDX6	ENST00000526070.2	TSL:1	c.1175-4delT	splice_region intron	N/A	ENSP00000433704.1	P26196
DDX6	ENST00000620157.4	TSL:1	c.1175-4delT	splice_region intron	N/A	ENSP00000478754.1	P26196

Frequencies

GnomAD3 genomes

AF:

0.000334

AC:

AN:

146848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000746

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000408

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0186

AC:

2355

AN:

126892

AF XY:

0.0182

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.0227

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0265

GnomAD4 exome

AF:

0.0193

AC:

19569

AN:

1013454

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

9452

AN XY:

504812

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0217

AC:

495

AN:

22782

American (AMR)

AF:

0.0164

AC:

477

AN:

29076

Ashkenazi Jewish (ASJ)

AF:

0.0183

AC:

305

AN:

16664

East Asian (EAS)

AF:

0.00955

AC:

250

AN:

26180

South Asian (SAS)

AF:

0.0189

AC:

1063

AN:

56110

European-Finnish (FIN)

AF:

0.0148

AC:

534

AN:

36198

Middle Eastern (MID)

AF:

0.0133

AC:

AN:

4300

European-Non Finnish (NFE)

AF:

0.0200

AC:

15642

AN:

781614

Other (OTH)

AF:

0.0184

AC:

746

AN:

40530

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

2739

5478

8216

10955

13694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

684

1368

2052

2736

3420

<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:

0.000333

AC:

AN:

146934

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

AN XY:

71422

show subpopulations

African (AFR)

AF:

0.000744

AC:

AN:

40304

American (AMR)

AF:

0.000407

AC:

AN:

14730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.000392

AC:

AN:

5108

South Asian (SAS)

AF:

0.00

AC:

AN:

4674

European-Finnish (FIN)

AF:

0.000109

AC:

AN:

9206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000151

AC:

AN:

66294

Other (OTH)

AF:

0.00

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0322

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.061

Mutation Taster

=100/0

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.

11-118755506-TAAAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over