Genetic Variant DDX6:c.1175-7_1175-4dupTTTT (chr11-118755506-T-TAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004397.6(DDX6):c.1175-7_1175-4dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

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: Uncertain_significance. The variant received 0 ACMG points.

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.1175-7_1175-4dupTTTT	splice_region intron	N/A	NP_004388.2	P26196
DDX6	NM_001257191.3		c.1175-7_1175-4dupTTTT	splice_region intron	N/A	NP_001244120.1	P26196
DDX6	NM_001425145.1		c.1175-7_1175-4dupTTTT	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.1175-4_1175-3insTTTT	splice_region intron	N/A	ENSP00000442266.1	P26196
DDX6	ENST00000526070.2	TSL:1	c.1175-4_1175-3insTTTT	splice_region intron	N/A	ENSP00000433704.1	P26196
DDX6	ENST00000620157.4	TSL:1	c.1175-4_1175-3insTTTT	splice_region intron	N/A	ENSP00000478754.1	P26196

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146976

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1092820

Hom.:

Cov.:

AF XY:

0.00000183

AC XY:

AN XY:

546826

show subpopulations

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

African (AFR)

AF:

0.0000406

AC:

AN:

24634

American (AMR)

AF:

0.00

AC:

AN:

32238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18892

East Asian (EAS)

AF:

0.00

AC:

AN:

29402

South Asian (SAS)

AF:

0.00

AC:

AN:

63204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4562

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

835928

Other (OTH)

AF:

0.00

AC:

AN:

44292

⚠️ 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: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

146976

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71396

African (AFR)

AF:

0.00

AC:

AN:

40216

American (AMR)

AF:

0.00

AC:

AN:

14730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3404

East Asian (EAS)

AF:

0.00

AC:

AN:

5126

South Asian (SAS)

AF:

0.00

AC:

AN:

4676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66352

Other (OTH)

AF:

0.00

AC:

AN:

2020

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.061

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over