11-125904156-C-T

Variant names:

• chr11-125904156-C-T
• rs1124708
• NM_001330438.2:c.-280+726C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001330438.2(DDX25):​c.-280+726C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,142 control chromosomes in the GnomAD database, including 28,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28445 hom., cov: 34)
• Consequence: DDX25 NM_001330438.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.269
• Publications: 2 publications found

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]

DDX25 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

DDX25-AS1 (HGNC:58188):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 11-125904156-C-T is Benign according to our data. Variant chr11-125904156-C-T is described in ClinVar as Benign. ClinVar VariationId is 1295373.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330438.2. 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
	DDX25	NM_001330438.2		c.-280+726C>T		intron	N/A	NP_001317367.1	A0A384NYS3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX25	ENST00000525943.1	TSL:5	c.-280+726C>T		intron	N/A	ENSP00000490224.1	Q9UHL0-2
	DDX25-AS1	ENST00000533033.2	TSL:4	n.395-787G>A		intron	N/A
	DDX25	ENST00000637851.1	TSL:5	n.-213+726C>T		intron	N/A	ENSP00000490392.1	A0A1B0GV69

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92653 AN: 152026 Hom.: 28421 Cov.: 34

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.598

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.609 AC: 92730 AN: 152142 Hom.: 28445 Cov.: 34 AF XY: 0.613 AC XY: 45570 AN XY: 74382

African (AFR) AF: 0.544 AC: 22604 AN: 41526

American (AMR) AF: 0.676 AC: 10346 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2286 AN: 3470

East Asian (EAS) AF: 0.697 AC: 3591 AN: 5154

South Asian (SAS) AF: 0.712 AC: 3431 AN: 4820

European-Finnish (FIN) AF: 0.606 AC: 6414 AN: 10588

Middle Eastern (MID) AF: 0.603 AC: 176 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42123 AN: 67966

Other (OTH) AF: 0.600 AC: 1269 AN: 2114

Alfa AF: 0.542 Hom.: 2310

Bravo AF: 0.608

Asia WGS AF: 0.696 AC: 2415 AN: 3474

ClinVar

ClinVar submissions

Significance: 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	-0.70
CADD	Benign	8.1
DANN	Benign	0.85
PhyloP100		-0.27
PromoterAI		0.00010	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1124708; hg19: chr11-125774051; COSMIC: COSV54992685; COSMIC: COSV54992685;