11-118754900-C-T

Position:

• chr11-118754900-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1277-13G>A		intron_variant		ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1277-13G>A		intron_variant		1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1277-13G>A		intron_variant		1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1277-13G>A		intron_variant		1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.880-13G>A		intron_variant		2

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

GnomAD3 exomes AF: 0.890 AC: 195282 AN: 219298 Hom.: 87151 AF XY: 0.889 AC XY: 106224 AN XY: 119486

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 SAS exome AF: 0.887

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

Gnomad4 AFR exome AF: 0.788

Gnomad4 AMR exome AF: 0.924

Gnomad4 ASJ exome AF: 0.899

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.906

Gnomad4 NFE exome AF: 0.868

Gnomad4 OTH exome AF: 0.873

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

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.873

Alfa AF: 0.870 Hom.: 10448

Bravo AF: 0.860

Asia WGS AF: 0.934 AC: 3250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Intellectual developmental disorder with impaired language and dysmorphic facies Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs580079; hg19: chr11-118625609;