rs6589689

Variant names:

• chr11-118752035-G-A
• rs6589689
• NM_004397.6:c.*70C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-118752035-G-A
• chr11-118752035-G-C
• chr11-118752035-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_004397.6(DDX6):​c.*70C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.989 in 282,990 control chromosomes in the GnomAD database, including 138,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74623 hom., cov: 32)
  • Exomes 𝑓: 0.99 (63880 hom.)
• Consequence: DDX6 NM_004397.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.14
• Publications: 6 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

ENSG00000308658 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-118752035-G-A is Benign according to our data. Variant chr11-118752035-G-A is described in ClinVar as Benign. ClinVar VariationId is 1300455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 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.*70C>T		3_prime_UTR	Exon 14 of 14	NP_004388.2	P26196
	DDX6	NM_001257191.3		c.*70C>T		3_prime_UTR	Exon 14 of 14	NP_001244120.1	P26196
	DDX6	NM_001425145.1		c.*70C>T		3_prime_UTR	Exon 14 of 14	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.*70C>T		3_prime_UTR	Exon 14 of 14	ENSP00000442266.1	P26196
	DDX6	ENST00000620157.4	TSL:1	c.*70C>T		3_prime_UTR	Exon 14 of 14	ENSP00000478754.1	P26196
	DDX6	ENST00000953098.1		c.*70C>T		3_prime_UTR	Exon 14 of 14	ENSP00000623157.1

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150637 AN: 152186 Hom.: 74562 Cov.: 32

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.991

GnomAD4 exome AF: 0.989 AC: 129208 AN: 130686 Hom.: 63880 Cov.: 0 AF XY: 0.989 AC XY: 73623 AN XY: 74428

African (AFR) AF: 0.997 AC: 2175 AN: 2182

American (AMR) AF: 0.994 AC: 4118 AN: 4144

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3518 AN: 3530

East Asian (EAS) AF: 1.00 AC: 3446 AN: 3446

South Asian (SAS) AF: 0.993 AC: 27515 AN: 27706

European-Finnish (FIN) AF: 0.983 AC: 7121 AN: 7246

Middle Eastern (MID) AF: 0.995 AC: 2089 AN: 2100

European-Non Finnish (NFE) AF: 0.986 AC: 72831 AN: 73868

Other (OTH) AF: 0.989 AC: 6395 AN: 6464

GnomAD4 genome AF: 0.990 AC: 150757 AN: 152304 Hom.: 74623 Cov.: 32 AF XY: 0.989 AC XY: 73695 AN XY: 74478

African (AFR) AF: 0.997 AC: 41449 AN: 41560

American (AMR) AF: 0.993 AC: 15175 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3453 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 0.992 AC: 4792 AN: 4830

European-Finnish (FIN) AF: 0.976 AC: 10370 AN: 10620

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67037 AN: 68036

Other (OTH) AF: 0.991 AC: 2095 AN: 2114

Alfa AF: 0.988 Hom.: 64032

Bravo AF: 0.991

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs6589689; hg19: chr11-118622744;