12-31083962-C-T

Variant names:

• chr12-31083962-C-T
• rs141393116
• NM_030653.4:c.294C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001413702.1(DDX11):​c.-230-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,613,836 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: DDX11 NM_001413702.1 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.436
• Publications: 0 publications found

Genes affected

DDX11 (HGNC:2736): (DEAD/H-box helicase 11) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

DDX11 Gene-Disease associations (from GenCC):

• Warsaw breakage syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 12-31083962-C-T is Benign according to our data. Variant chr12-31083962-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3239129.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001413702.1. 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
	DDX11	NM_030653.4	MANE Select	c.294C>T	p.Cys98Cys	synonymous	Exon 3 of 27	NP_085911.2	Q96FC9-2
	DDX11	NM_001257144.2		c.294C>T	p.Cys98Cys	synonymous	Exon 3 of 27	NP_001244073.1	Q96FC9-1
	DDX11	NM_001413695.1		c.294C>T	p.Cys98Cys	synonymous	Exon 5 of 29	NP_001400624.1	Q96FC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX11	ENST00000542838.6	TSL:1 MANE Select	c.294C>T	p.Cys98Cys	synonymous	Exon 3 of 27	ENSP00000443426.1	Q96FC9-2
	DDX11	ENST00000545668.5	TSL:1	c.294C>T	p.Cys98Cys	synonymous	Exon 3 of 27	ENSP00000440402.1	Q96FC9-1
	DDX11	ENST00000228264.10	TSL:1	c.216C>T	p.Cys72Cys	synonymous	Exon 3 of 27	ENSP00000228264.6	Q96FC9-3

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152164 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000390 AC: 98 AN: 251138 AF XY: 0.000332

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00635

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000244 AC: 357 AN: 1461672 Hom.: 1 Cov.: 33 AF XY: 0.000241 AC XY: 175 AN XY: 727146

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.000268 AC: 12 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00578 AC: 151 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.000123 AC: 137 AN: 1111842

Other (OTH) AF: 0.000745 AC: 45 AN: 60378

GnomAD4 genome AF: 0.000283 AC: 43 AN: 152164 Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.000131 AC: 2 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68028

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000715 Hom.: 0

Bravo AF: 0.000272

EpiCase AF: 0.000164

EpiControl AF: 0.000474

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.7
DANN	Benign	0.62
PhyloP100		0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs141393116; hg19: chr12-31236896;