NM_004397.6:c.1175-6_1175-4dupTTT

Variant names:

• chr11-118755506-T-TAAA
• rs551201488
• NM_004397.6:c.1175-6_1175-4dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004397.6(DDX6):​c.1175-6_1175-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,092,776 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: DDX6 NM_004397.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1175-6_1175-4dupTTT		splice_region intron	N/A	NP_004388.2	P26196
	DDX6	NM_001257191.3		c.1175-6_1175-4dupTTT		splice_region intron	N/A	NP_001244120.1	P26196
	DDX6	NM_001425145.1		c.1175-6_1175-4dupTTT		splice_region 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.1175-4_1175-3insTTT		splice_region intron	N/A	ENSP00000442266.1	P26196
	DDX6	ENST00000526070.2	TSL:1	c.1175-4_1175-3insTTT		splice_region intron	N/A	ENSP00000433704.1	P26196
	DDX6	ENST00000620157.4	TSL:1	c.1175-4_1175-3insTTT		splice_region intron	N/A	ENSP00000478754.1	P26196

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000366 AC: 4 AN: 1092776 Hom.: 0 Cov.: 18 AF XY: 0.00000183 AC XY: 1 AN XY: 546806

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24636

American (AMR) AF: 0.00 AC: 0 AN: 32236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18892

East Asian (EAS) AF: 0.00 AC: 0 AN: 29402

South Asian (SAS) AF: 0.00 AC: 0 AN: 63198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4562

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 835894

Other (OTH) AF: 0.0000452 AC: 2 AN: 44290

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.061

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs551201488; hg19: chr11-118626215;