11-118755506-T-TA

Variant names:

• chr11-118755506-T-TA
• rs551201488
• NM_004397.6:c.1175-4dupT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_004397.6(DDX6):​c.1175-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,145,874 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1 hom.)
• Consequence: DDX6 NM_004397.6 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0610

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 11-118755506-T-TA is Benign according to our data. Variant chr11-118755506-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 3059409.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0338 (33776/998890) while in subpopulation NFE AF= 0.0351 (27108/773170). AF 95% confidence interval is 0.0347. There are 1 homozygotes in gnomad4_exome. There are 16519 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 137 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1175-4dupT		splice_region_variant, intron_variant	Intron 11 of 13	ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1175-4_1175-3insT		splice_region_variant, intron_variant	Intron 11 of 13	1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1175-4_1175-3insT		splice_region_variant, intron_variant	Intron 11 of 12	1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1175-4_1175-3insT		splice_region_variant, intron_variant	Intron 11 of 13	1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.778-4_778-3insT		splice_region_variant, intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes AF: 0.000939 AC: 138 AN: 146898 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000895

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.00128

Gnomad FIN AF: 0.000759

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000995

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0338 AC: 33776 AN: 998890 Hom.: 1 Cov.: 18 AF XY: 0.0333 AC XY: 16519 AN XY: 496488

Gnomad4 AFR exome AF: 0.0308

Gnomad4 AMR exome AF: 0.0254

Gnomad4 ASJ exome AF: 0.0314

Gnomad4 EAS exome AF: 0.0250

Gnomad4 SAS exome AF: 0.0308

Gnomad4 FIN exome AF: 0.0259

Gnomad4 NFE exome AF: 0.0351

Gnomad4 OTH exome AF: 0.0358

GnomAD4 genome AF: 0.000932 AC: 137 AN: 146984 Hom.: 0 Cov.: 32 AF XY: 0.000952 AC XY: 68 AN XY: 71446

Gnomad4 AFR AF: 0.000893

Gnomad4 AMR AF: 0.00102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00137

Gnomad4 SAS AF: 0.00128

Gnomad4 FIN AF: 0.000759

Gnomad4 NFE AF: 0.000995

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DDX6-related disorder Benign:1

Apr 29, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs551201488; hg19: chr11-118626215;