dbSNP rs551201488: DDX6:c.1175-7_1175-4delTTTT (chr11-118755506-TAAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004397.6(DDX6):c.1175-7_1175-4delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000915 in 1,092,834 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

DDX6
NM_004397.6 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.36

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000788

AC:

AN:

126892

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000721

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1092834

Hom.:

AF XY:

0.00

AC XY:

AN XY:

546832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24636

American (AMR)

AF:

0.0000310

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:

835940

Other (OTH)

AF:

0.00

AC:

AN:

44292

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

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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