11-125904535-G-C

Position:

• chr11-125904535-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013264.5(DDX25):​c.18G>C​(p.Trp6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX25 NM_013264.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31900385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX25	NM_013264.5	c.18G>C	p.Trp6Cys	missense_variant	1/12	ENST00000263576.11	NP_037396.3
DDX25	XM_047426849.1	c.18G>C	p.Trp6Cys	missense_variant	1/11		XP_047282805.1
DDX25	NM_001330438.2	c.-279-677G>C		intron_variant			NP_001317367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX25	ENST00000263576.11	c.18G>C	p.Trp6Cys	missense_variant	1/12	1	NM_013264.5	ENSP00000263576.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2023

The c.18G>C (p.W6C) alteration is located in exon 1 (coding exon 1) of the DDX25 gene. This alteration results from a G to C substitution at nucleotide position 18, causing the tryptophan (W) at amino acid position 6 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Benign	0.92
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		0.70	P;.
Vest4		0.45
MutPred		0.64		Loss of catalytic residue at L4 (P = 0.003);.;
MVP		0.37
MPC		0.89
ClinPred		0.92	D
GERP RS		3.2
Varity_R		0.31
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1016153260; hg19: chr11-125774430;