chr12-31092807-A-G

Variant names:

• chr12-31092807-A-G
• rs2075321
• NM_030653.4:c.1243-39A>G

Variant summary

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

The NM_030653.4(DDX11):​c.1243-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,575,780 control chromosomes in the GnomAD database, including 189,227 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (23194 hom., cov: 32)
  • Exomes 𝑓: 0.47 (166033 hom.)
• Consequence: DDX11 NM_030653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 12 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=-0.93).
• 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: NM_030653.4. 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.1243-39A>G		intron	N/A	NP_085911.2
	DDX11	NM_001257144.2		c.1243-39A>G		intron	N/A	NP_001244073.1
	DDX11	NM_001413695.1		c.1243-39A>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.1243-39A>G		intron	N/A	ENSP00000443426.1
	DDX11	ENST00000545668.5	TSL:1	c.1243-39A>G		intron	N/A	ENSP00000440402.1
	DDX11	ENST00000228264.10	TSL:1	c.1165-39A>G		intron	N/A	ENSP00000228264.6

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81573 AN: 151726 Hom.: 23140 Cov.: 32

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.519

GnomAD2 exomes AF: 0.527 AC: 131374 AN: 249468 AF XY: 0.517

Gnomad AFR exome AF: 0.690

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.811

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.439

Gnomad OTH exome AF: 0.494

GnomAD4 exome AF: 0.472 AC: 672568 AN: 1423938 Hom.: 166033 Cov.: 30 AF XY: 0.474 AC XY: 336085 AN XY: 709584

African (AFR) AF: 0.680 AC: 22042 AN: 32414

American (AMR) AF: 0.652 AC: 29073 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 10359 AN: 25860

East Asian (EAS) AF: 0.848 AC: 33404 AN: 39402

South Asian (SAS) AF: 0.566 AC: 48360 AN: 85380

European-Finnish (FIN) AF: 0.420 AC: 22373 AN: 53316

Middle Eastern (MID) AF: 0.493 AC: 2750 AN: 5580

European-Non Finnish (NFE) AF: 0.441 AC: 475187 AN: 1078370

Other (OTH) AF: 0.492 AC: 29020 AN: 59042

GnomAD4 genome AF: 0.538 AC: 81682 AN: 151842 Hom.: 23194 Cov.: 32 AF XY: 0.540 AC XY: 40083 AN XY: 74218

African (AFR) AF: 0.679 AC: 28106 AN: 41420

American (AMR) AF: 0.596 AC: 9101 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1340 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4209 AN: 5142

South Asian (SAS) AF: 0.570 AC: 2749 AN: 4826

European-Finnish (FIN) AF: 0.417 AC: 4402 AN: 10554

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30142 AN: 67850

Other (OTH) AF: 0.518 AC: 1088 AN: 2100

Alfa AF: 0.475 Hom.: 3210

Bravo AF: 0.561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.59
DANN	Benign	0.54
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075321; hg19: chr12-31245741; COSMIC: COSV52500101; COSMIC: COSV52500101;