11-118757229-G-A

Variant names:

• chr11-118757229-G-A
• NM_004397.6:c.1052C>T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_004397.6(DDX6):​c.1052C>T​(p.Ala351Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX6 NM_004397.6 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.92

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.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837
• PP5: Variant 11-118757229-G-A is Pathogenic according to our data. Variant chr11-118757229-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1803958.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1052C>T	p.Ala351Val	missense_variant	Exon 10 of 14	ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1052C>T	p.Ala351Val	missense_variant	Exon 10 of 14	1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1052C>T	p.Ala351Val	missense_variant	Exon 10 of 13	1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1052C>T	p.Ala351Val	missense_variant	Exon 10 of 14	1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.655C>T		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Jan 05, 2022

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.57	D;D;D
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;.;.
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-4.0	.;D;D
REVEL	Uncertain	0.57
Sift	Benign	0.037	.;D;D
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.79
MutPred		0.50		Gain of MoRF binding (P = 0.1692);Gain of MoRF binding (P = 0.1692);Gain of MoRF binding (P = 0.1692);
MVP		0.68
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.82

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: chr11-118627938;