11-125908556-T-A

Position:

• chr11-125908556-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013264.5(DDX25):​c.507+53T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,486,650 control chromosomes in the GnomAD database, including 17,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1498 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16414 hom.)
• Consequence: DDX25 NM_013264.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.235

Genes affected

DDX25 (HGNC:18698): (DEAD-box helicase 25) 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 the DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The encoded protein is a gonadotropin-regulated and developmentally expressed testicular RNA helicase. It may serve to maintain testicular functions related to steroidogenesis and spermatogenesis. [provided by RefSeq, Jul 2008]

ENSG00000255027 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-125908556-T-A is Benign according to our data. Variant chr11-125908556-T-A is described in ClinVar as [Benign]. Clinvar id is 1182265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX25	NM_013264.5	c.507+53T>A		intron_variant		ENST00000263576.11	NP_037396.3
DDX25	NM_001330438.2	c.165+53T>A		intron_variant			NP_001317367.1
DDX25	XM_047426849.1	c.507+53T>A		intron_variant			XP_047282805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX25	ENST00000263576.11	c.507+53T>A		intron_variant		1	NM_013264.5	ENSP00000263576.6

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18760 AN: 152056 Hom.: 1496 Cov.: 32

Gnomad AFR AF: 0.0461

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.152 AC: 202299 AN: 1334476 Hom.: 16414 AF XY: 0.152 AC XY: 101779 AN XY: 670722

Gnomad4 AFR exome AF: 0.0407

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.185

Gnomad4 SAS exome AF: 0.187

Gnomad4 FIN exome AF: 0.0983

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.123 AC: 18762 AN: 152174 Hom.: 1498 Cov.: 32 AF XY: 0.124 AC XY: 9230 AN XY: 74392

Gnomad4 AFR AF: 0.0460

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0894

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.128

Alfa AF: 0.122 Hom.: 156

Bravo AF: 0.129

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.79

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: rs551365; hg19: chr11-125778451; COSMIC: COSV54990819;