11-118756319-T-C

Variant names:

• chr11-118756319-T-C
• rs1591885401
• NM_004397.6:c.1115A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_004397.6(DDX6):​c.1115A>G​(p.His372Arg) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DDX6 NM_004397.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.80

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-118756319-T-C is Pathogenic according to our data. Variant chr11-118756319-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 694353.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1115A>G	p.His372Arg	missense_variant	Exon 11 of 14	ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1115A>G	p.His372Arg	missense_variant	Exon 11 of 14	1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1115A>G	p.His372Arg	missense_variant	Exon 11 of 13	1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1115A>G	p.His372Arg	missense_variant	Exon 11 of 14	1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.718A>G		non_coding_transcript_exon_variant	Exon 3 of 6	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Nov 08, 2019

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D;D
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;.;.
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	-0.84	N;N;N
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-7.2	.;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.015	.;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.90	P;P;P
Vest4		0.71
MutPred		0.43		Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);
MVP		0.91
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.90

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: rs1591885401; hg19: chr11-118627028;