rs1568112229

Variant names:

• chr17-64506521-T-C
• rs1568112229
• ENST00000578491.2:n.1A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-64506521-T-C
• chr17-64506521-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000578491.2(DDX5):​n.1A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000181 in 551,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: DDX5 ENST00000578491.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.570
• Publications: 0 publications found

Genes affected

DDX5 (HGNC:2746): (DEAD-box helicase 5) This gene encodes a member of the DEAD box family of RNA helicases that are involved in a variety of cellular processes as a result of its role as an adaptor molecule, promoting interactions with a large number of other factors. This protein is involved in pathways that include the alteration of RNA structures, plays a role as a coregulator of transcription, a regulator of splicing, and in the processing of small noncoding RNAs. Members of this family contain nine conserved motifs, including the conserved Asp-Glu-Ala-Asp (DEAD) motif, important to ATP binding and hydrolysis as well as RNA binding and unwinding activities. Dysregulation of this gene may play a role in cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2017]

CEP95 (HGNC:25141): (centrosomal protein 95) Located in centrosome and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX5	NM_004396.5	c.-402A>G		upstream_gene_variant		ENST00000225792.10	NP_004387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX5	ENST00000225792.10	c.-402A>G		upstream_gene_variant		1	NM_004396.5	ENSP00000225792.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000181 AC: 1 AN: 551276 Hom.: 0 Cov.: 8 AF XY: 0.00000366 AC XY: 1 AN XY: 272870

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14926

American (AMR) AF: 0.00 AC: 0 AN: 12962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11452

East Asian (EAS) AF: 0.00 AC: 0 AN: 20444

South Asian (SAS) AF: 0.00 AC: 0 AN: 42580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1790

European-Non Finnish (NFE) AF: 0.00000243 AC: 1 AN: 410962

Other (OTH) AF: 0.00 AC: 0 AN: 25794

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		0.57
PromoterAI		0.15	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1568112229; hg19: chr17-62502639;