11-125904265-TCGCCCCGCTCTCTGCCCTC-T

Variant names:

• chr11-125904265-TCGCCCCGCTCTCTGCCCTC-T
• rs201190482
• NM_001330438.2:c.-280+872_-280+890delTCCGCCCCGCTCTCTGCCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001330438.2(DDX25):​c.-280+872_-280+890delTCCGCCCCGCTCTCTGCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 338,436 control chromosomes in the GnomAD database, including 67,975 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29117 hom., cov: 0)
  • Exomes 𝑓: 0.63 (38858 hom.)
• Consequence: DDX25 NM_001330438.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.661
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 11-125904265-TCGCCCCGCTCTCTGCCCTC-T is Benign according to our data. Variant chr11-125904265-TCGCCCCGCTCTCTGCCCTC-T is described in ClinVar as Benign. ClinVar VariationId is 1250886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.697 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+872_-280+890delTCCGCCCCGCTCTCTGCCC		intron	N/A	NP_001317367.1	A0A384NYS3
	DDX25	NM_013264.5	MANE Select	c.-252_-234delCGCCCCGCTCTCTGCCCTC		upstream_gene	N/A	NP_037396.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX25	ENST00000525943.1	TSL:5	c.-280+836_-280+854delCGCCCCGCTCTCTGCCCTC		intron	N/A	ENSP00000490224.1	Q9UHL0-2
	DDX25-AS1	ENST00000533033.2	TSL:4	n.395-915_395-897delGAGGGCAGAGAGCGGGGCG		intron	N/A
	DDX25	ENST00000637851.1	TSL:5	n.-213+836_-213+854delCGCCCCGCTCTCTGCCCTC		intron	N/A	ENSP00000490392.1	A0A1B0GV69

Frequencies

GnomAD3 genomes AF: 0.622 AC: 92696 AN: 149036 Hom.: 29091 Cov.: 0

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.628

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.614

GnomAD4 exome AF: 0.634 AC: 120033 AN: 189294 Hom.: 38858 AF XY: 0.635 AC XY: 61468 AN XY: 96864

African (AFR) AF: 0.551 AC: 2850 AN: 5176

American (AMR) AF: 0.691 AC: 3750 AN: 5430

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 4477 AN: 6802

East Asian (EAS) AF: 0.722 AC: 12682 AN: 17570

South Asian (SAS) AF: 0.714 AC: 1334 AN: 1868

European-Finnish (FIN) AF: 0.613 AC: 10437 AN: 17038

Middle Eastern (MID) AF: 0.593 AC: 570 AN: 962

European-Non Finnish (NFE) AF: 0.624 AC: 76313 AN: 122244

Other (OTH) AF: 0.624 AC: 7620 AN: 12204

GnomAD4 genome AF: 0.622 AC: 92771 AN: 149142 Hom.: 29117 Cov.: 0 AF XY: 0.623 AC XY: 45357 AN XY: 72746

African (AFR) AF: 0.553 AC: 22245 AN: 40248

American (AMR) AF: 0.686 AC: 10337 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2301 AN: 3434

East Asian (EAS) AF: 0.692 AC: 3390 AN: 4896

South Asian (SAS) AF: 0.717 AC: 3371 AN: 4700

European-Finnish (FIN) AF: 0.607 AC: 6241 AN: 10274

Middle Eastern (MID) AF: 0.631 AC: 183 AN: 290

European-Non Finnish (NFE) AF: 0.638 AC: 42941 AN: 67276

Other (OTH) AF: 0.616 AC: 1261 AN: 2046

Alfa AF: 0.445 Hom.: 940

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
PhyloP100		0.66

Splicing

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

Other links and lift over

dbSNP: rs201190482; hg19: chr11-125774160; COSMIC: COSV54993464; COSMIC: COSV54993464;