11-118755477-G-C

Position:

• chr11-118755477-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP2

The NM_004397.6(DDX6):​c.1201C>G​(p.Gln401Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX6 NM_004397.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.86

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 Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a domain Helicase C-terminal (size 160) in uniprot entity DDX6_HUMAN there are 8 pathogenic changes around while only 0 benign (100%) in NM_004397.6
• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DDX6. . Trascript score misZ 4.2715 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, intellectual developmental disorder with impaired language and dysmorphic facies.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX6	NM_004397.6	c.1201C>G	p.Gln401Glu	missense_variant	12/14	ENST00000534980.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX6	ENST00000534980.7	c.1201C>G	p.Gln401Glu	missense_variant	12/14	1	NM_004397.6	P1
DDX6	ENST00000526070.2	c.1201C>G	p.Gln401Glu	missense_variant	12/13	1		P1
DDX6	ENST00000620157.4	c.1201C>G	p.Gln401Glu	missense_variant	12/14	1		P1
DDX6	ENST00000529162.1	n.804C>G		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 30, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;D;D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;.;.
M_CAP	Benign	0.0065	T
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.77	N;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.9	.;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.023	.;D;D
Sift4G	Uncertain	0.039	D;D;D
Polyphen		0.98	D;D;D
Vest4		0.70
MutPred		0.57		Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);
MVP		0.61
ClinPred		0.95	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.86
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118626186;