11-118754828-G-C

Variant names:

• chr11-118754828-G-C
• NM_004397.6:c.1336C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004397.6(DDX6):​c.1336C>G​(p.Leu446Val) 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: 10.0

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX6	NM_004397.6	c.1336C>G	p.Leu446Val	missense_variant	Exon 13 of 14	ENST00000534980.7	NP_004388.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX6	ENST00000534980.7	c.1336C>G	p.Leu446Val	missense_variant	Exon 13 of 14	1	NM_004397.6	ENSP00000442266.1
DDX6	ENST00000526070.2	c.1336C>G	p.Leu446Val	missense_variant	Exon 13 of 13	1		ENSP00000433704.1
DDX6	ENST00000620157.4	c.1336C>G	p.Leu446Val	missense_variant	Exon 13 of 14	1		ENSP00000478754.1
DDX6	ENST00000529162.1	n.939C>G		non_coding_transcript_exon_variant	Exon 5 of 6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Feb 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1336C>G (p.L446V) alteration is located in exon 13 (coding exon 12) of the DDX6 gene. This alteration results from a C to G substitution at nucleotide position 1336, causing the leucine (L) at amino acid position 446 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D;.;.
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.0	L;L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.7	.;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.020	.;D;D
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.94	P;P;P
Vest4		0.69
MutPred		0.64		Loss of stability (P = 0.019);Loss of stability (P = 0.019);Loss of stability (P = 0.019);
MVP		0.74
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.92

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: chr11-118625537;