rs580079

Variant names:

• chr11-118754900-C-T
• rs580079
• NM_004397.6:c.1277-13G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004397.6(DDX6):​c.1277-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,584,662 control chromosomes in the GnomAD database, including 604,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56897 hom., cov: 32)
  • Exomes 𝑓: 0.87 (547744 hom.)
• Consequence: DDX6 NM_004397.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.316
• Publications: 13 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: G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308658 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-118754900-C-T is Benign according to our data. Variant chr11-118754900-C-T is described in ClinVar as Benign. ClinVar VariationId is 1255475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.1277-13G>A		intron	N/A	NP_004388.2	P26196
	DDX6	NM_001257191.3		c.1277-13G>A		intron	N/A	NP_001244120.1	P26196
	DDX6	NM_001425145.1		c.1277-13G>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.1277-13G>A		intron	N/A	ENSP00000442266.1	P26196
	DDX6	ENST00000526070.2	TSL:1	c.1277-13G>A		intron	N/A	ENSP00000433704.1	P26196
	DDX6	ENST00000620157.4	TSL:1	c.1277-13G>A		intron	N/A	ENSP00000478754.1	P26196

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131259 AN: 152058 Hom.: 56849 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.872

GnomAD2 exomes AF: 0.890 AC: 195282 AN: 219298 AF XY: 0.889

Gnomad AFR exome AF: 0.798

Gnomad AMR exome AF: 0.927

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.905

Gnomad NFE exome AF: 0.874

Gnomad OTH exome AF: 0.888

GnomAD4 exome AF: 0.874 AC: 1251848 AN: 1432486 Hom.: 547744 Cov.: 34 AF XY: 0.874 AC XY: 622495 AN XY: 712092

African (AFR) AF: 0.788 AC: 24851 AN: 31542

American (AMR) AF: 0.924 AC: 32822 AN: 35512

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 22176 AN: 24666

East Asian (EAS) AF: 1.00 AC: 39437 AN: 39446

South Asian (SAS) AF: 0.882 AC: 71436 AN: 81038

European-Finnish (FIN) AF: 0.906 AC: 47775 AN: 52752

Middle Eastern (MID) AF: 0.821 AC: 4595 AN: 5596

European-Non Finnish (NFE) AF: 0.868 AC: 957165 AN: 1102868

Other (OTH) AF: 0.873 AC: 51591 AN: 59066

GnomAD4 genome AF: 0.863 AC: 131363 AN: 152176 Hom.: 56897 Cov.: 32 AF XY: 0.864 AC XY: 64273 AN XY: 74386

African (AFR) AF: 0.801 AC: 33244 AN: 41496

American (AMR) AF: 0.900 AC: 13757 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3114 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5178 AN: 5182

South Asian (SAS) AF: 0.894 AC: 4317 AN: 4828

European-Finnish (FIN) AF: 0.895 AC: 9482 AN: 10590

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59338 AN: 68004

Other (OTH) AF: 0.873 AC: 1842 AN: 2110

Alfa AF: 0.868 Hom.: 10714

Bravo AF: 0.860

Asia WGS AF: 0.934 AC: 3250 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Intellectual developmental disorder with impaired language and dysmorphic facies (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		-0.32
Mutation Taster		=22/78	disease causing

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: rs580079; hg19: chr11-118625609;