12-31091912-C-G

Variant names:

• chr12-31091912-C-G
• rs1808348
• NM_030653.4:c.1242+41C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000542838.6(DDX11):​c.1242+41C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,612,608 control chromosomes in the GnomAD database, including 198,157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.54 (23491 hom., cov: 34)
  • Exomes 𝑓: 0.48 (174666 hom.)
• Consequence: DDX11 ENST00000542838.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 22 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542838.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX11	NM_030653.4	MANE Select	c.1242+41C>G		intron	N/A	NP_085911.2
	DDX11	NM_001257144.2		c.1242+41C>G		intron	N/A	NP_001244073.1
	DDX11	NM_001413695.1		c.1242+41C>G		intron	N/A	NP_001400624.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX11	ENST00000542838.6	TSL:1 MANE Select	c.1242+41C>G		intron	N/A	ENSP00000443426.1
	DDX11	ENST00000545668.5	TSL:1	c.1242+41C>G		intron	N/A	ENSP00000440402.1
	DDX11	ENST00000228264.10	TSL:1	c.1164+41C>G		intron	N/A	ENSP00000228264.6

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82333 AN: 152074 Hom.: 23436 Cov.: 34

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.526

GnomAD2 exomes AF: 0.530 AC: 131762 AN: 248752 AF XY: 0.520

Gnomad AFR exome AF: 0.687

Gnomad AMR exome AF: 0.665

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.811

Gnomad FIN exome AF: 0.423

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.481 AC: 702848 AN: 1460416 Hom.: 174666 Cov.: 39 AF XY: 0.482 AC XY: 350037 AN XY: 726572

African (AFR) AF: 0.685 AC: 22909 AN: 33462

American (AMR) AF: 0.655 AC: 29246 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 10554 AN: 26114

East Asian (EAS) AF: 0.848 AC: 33637 AN: 39686

South Asian (SAS) AF: 0.568 AC: 48995 AN: 86220

European-Finnish (FIN) AF: 0.429 AC: 22735 AN: 53044

Middle Eastern (MID) AF: 0.499 AC: 2861 AN: 5736

European-Non Finnish (NFE) AF: 0.452 AC: 501813 AN: 1111142

Other (OTH) AF: 0.499 AC: 30098 AN: 60336

GnomAD4 genome AF: 0.542 AC: 82443 AN: 152192 Hom.: 23491 Cov.: 34 AF XY: 0.544 AC XY: 40463 AN XY: 74402

African (AFR) AF: 0.680 AC: 28225 AN: 41530

American (AMR) AF: 0.599 AC: 9163 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3468

East Asian (EAS) AF: 0.818 AC: 4230 AN: 5170

South Asian (SAS) AF: 0.572 AC: 2755 AN: 4818

European-Finnish (FIN) AF: 0.425 AC: 4497 AN: 10588

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30571 AN: 67996

Other (OTH) AF: 0.526 AC: 1112 AN: 2116

Alfa AF: 0.394 Hom.: 1796

Bravo AF: 0.564

Asia WGS AF: 0.696 AC: 2414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	12
DANN	Benign	0.46
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1808348; hg19: chr12-31244846;