NM_004397.6:c.*8-179A>G

Variant names:

• chr11-118752276-T-C
• rs3825057
• NM_004397.6:c.*8-179A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26
• Publications: 8 publications found

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

ENSG00000308658 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 31

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.: 31 AF XY: 0.225 AC XY: 16701 AN XY: 74340

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: 60 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16436 AN: 67972

Other (OTH) AF: 0.246 AC: 519 AN: 2114

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

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.19
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3825057; hg19: chr11-118622985;