11-125904062-G-C

Variant names:

• chr11-125904062-G-C
• rs1554526
• NM_001330438.2:c.-280+632G>C

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+632G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,212 control chromosomes in the GnomAD database, including 50,714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.81 (50714 hom., cov: 34)
• Consequence: DDX25 NM_001330438.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0150
• Publications: 4 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=-0.89).
• BP6: Variant 11-125904062-G-C is Benign according to our data. Variant chr11-125904062-G-C is described in ClinVar as Benign. ClinVar VariationId is 1266919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.876 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+632G>C		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+632G>C		intron	N/A	ENSP00000490224.1	Q9UHL0-2
	DDX25-AS1	ENST00000533033.2	TSL:4	n.395-693C>G		intron	N/A
	DDX25	ENST00000637851.1	TSL:5	n.-213+632G>C		intron	N/A	ENSP00000490392.1	A0A1B0GV69

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123215 AN: 152094 Hom.: 50673 Cov.: 34

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.810 AC: 123315 AN: 152212 Hom.: 50714 Cov.: 34 AF XY: 0.812 AC XY: 60422 AN XY: 74422

African (AFR) AF: 0.651 AC: 27024 AN: 41510

American (AMR) AF: 0.888 AC: 13593 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3022 AN: 3472

East Asian (EAS) AF: 0.882 AC: 4562 AN: 5172

South Asian (SAS) AF: 0.865 AC: 4175 AN: 4828

European-Finnish (FIN) AF: 0.851 AC: 9011 AN: 10594

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59366 AN: 68014

Other (OTH) AF: 0.809 AC: 1708 AN: 2110

Alfa AF: 0.838 Hom.: 6309

Bravo AF: 0.805

Asia WGS AF: 0.862 AC: 2997 AN: 3478

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	-0.89
CADD	Benign	5.3
DANN	Benign	0.50
PhyloP100		-0.015
PromoterAI		0.041	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1554526; hg19: chr11-125773957;