chr11-118748338-T-G

Variant names:

• chr11-118748338-T-G
• rs2077579
• NM_004397.6:c.*3767A>C

Variant summary

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

The NM_004397.6(DDX6):​c.*3767A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,896 control chromosomes in the GnomAD database, including 2,486 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 (2486 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: DDX6 NM_004397.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825
• Publications: 18 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

ENSG00000255422 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX6	NM_004397.6	MANE Select	c.*3767A>C		3_prime_UTR	Exon 14 of 14	NP_004388.2
	DDX6	NM_001257191.3		c.*3767A>C		3_prime_UTR	Exon 14 of 14	NP_001244120.1
	DDX6	NM_001425145.1		c.*3767A>C		3_prime_UTR	Exon 14 of 14	NP_001412074.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX6	ENST00000534980.7	TSL:1 MANE Select	c.*3767A>C		3_prime_UTR	Exon 14 of 14	ENSP00000442266.1
	DDX6	ENST00000620157.4	TSL:1	c.*3767A>C		3_prime_UTR	Exon 14 of 14	ENSP00000478754.1
	ENSG00000255422	ENST00000526274.2	TSL:3	n.374-1875T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26045 AN: 151778 Hom.: 2482 Cov.: 31

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.165

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.171 AC: 26049 AN: 151896 Hom.: 2486 Cov.: 31 AF XY: 0.174 AC XY: 12917 AN XY: 74230

African (AFR) AF: 0.0853 AC: 3533 AN: 41414

American (AMR) AF: 0.174 AC: 2649 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3470

East Asian (EAS) AF: 0.145 AC: 751 AN: 5162

South Asian (SAS) AF: 0.286 AC: 1376 AN: 4816

European-Finnish (FIN) AF: 0.223 AC: 2349 AN: 10536

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

European-Non Finnish (NFE) AF: 0.208 AC: 14135 AN: 67938

Other (OTH) AF: 0.164 AC: 346 AN: 2108

Alfa AF: 0.190 Hom.: 6984

Bravo AF: 0.159

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.77
PhyloP100		0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2077579; hg19: chr11-118619047;