11-118790689-C-T

Variant names:

• chr11-118790689-C-T
• rs57494551
• NM_004397.6:c.-268+409G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004397.6(DDX6):​c.-268+409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,038 control chromosomes in the GnomAD database, including 2,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2436 hom., cov: 30)
• Consequence: DDX6 NM_004397.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488
• Publications: 12 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 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.-268+409G>A		intron	N/A	NP_004388.2	P26196
	DDX6	NM_001257191.3		c.-268+166G>A		intron	N/A	NP_001244120.1	P26196
	DDX6	NM_001425145.1		c.-268+198G>A		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.-268+409G>A		intron	N/A	ENSP00000442266.1	P26196
	DDX6	ENST00000526070.2	TSL:1	c.-268+166G>A		intron	N/A	ENSP00000433704.1	P26196
	DDX6	ENST00000620157.4	TSL:1	c.-268+166G>A		intron	N/A	ENSP00000478754.1	P26196

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25642 AN: 151920 Hom.: 2431 Cov.: 30

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.169 AC: 25648 AN: 152038 Hom.: 2436 Cov.: 30 AF XY: 0.172 AC XY: 12750 AN XY: 74294

African (AFR) AF: 0.0779 AC: 3234 AN: 41504

American (AMR) AF: 0.171 AC: 2614 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3470

East Asian (EAS) AF: 0.145 AC: 741 AN: 5128

South Asian (SAS) AF: 0.289 AC: 1392 AN: 4824

European-Finnish (FIN) AF: 0.221 AC: 2346 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14092 AN: 67938

Other (OTH) AF: 0.160 AC: 338 AN: 2110

Alfa AF: 0.0962 Hom.: 193

Bravo AF: 0.156

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		0.49
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs57494551; hg19: chr11-118661398;