20-49235382-T-C

Variant names:

• chr20-49235382-T-C
• rs238150
• NM_017895.8:c.1427+294T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017895.8(DDX27):​c.1427+294T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 296,202 control chromosomes in the GnomAD database, including 7,281 homozygotes. 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: 𝑓 0.23 (4254 hom., cov: 32)
  • Exomes 𝑓: 0.20 (3027 hom.)
• Consequence: DDX27 NM_017895.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 15 publications found

Genes affected

DDX27 (HGNC:15837): (DEAD-box helicase 27) 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 this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein involved in the processing of 5.8S and 28S ribosomal RNAs. More specifically, the encoded protein localizes to the nucleolus, where it interacts with the PeBoW complex to ensure proper 3' end formation of 47S rRNA. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017895.8. 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
	DDX27	NM_017895.8	MANE Select	c.1427+294T>C		intron	N/A	NP_060365.8
	DDX27	NM_001348187.2		c.1520+294T>C		intron	N/A	NP_001335116.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX27	ENST00000618172.5	TSL:1 MANE Select	c.1427+294T>C		intron	N/A	ENSP00000482680.1
	DDX27	ENST00000471144.1	TSL:1	n.1545T>C		non_coding_transcript_exon	Exon 1 of 7
	DDX27	ENST00000484427.5	TSL:1	n.3048T>C		non_coding_transcript_exon	Exon 11 of 19

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34711 AN: 151972 Hom.: 4248 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0520

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.201 AC: 28929 AN: 144112 Hom.: 3027 Cov.: 3 AF XY: 0.198 AC XY: 14477 AN XY: 73114

African (AFR) AF: 0.310 AC: 1506 AN: 4860

American (AMR) AF: 0.166 AC: 873 AN: 5248

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 1022 AN: 5692

East Asian (EAS) AF: 0.0838 AC: 960 AN: 11450

South Asian (SAS) AF: 0.0880 AC: 311 AN: 3534

European-Finnish (FIN) AF: 0.209 AC: 2080 AN: 9940

Middle Eastern (MID) AF: 0.152 AC: 118 AN: 776

European-Non Finnish (NFE) AF: 0.217 AC: 20149 AN: 92818

Other (OTH) AF: 0.195 AC: 1910 AN: 9794

GnomAD4 genome AF: 0.228 AC: 34750 AN: 152090 Hom.: 4254 Cov.: 32 AF XY: 0.223 AC XY: 16563 AN XY: 74392

African (AFR) AF: 0.314 AC: 13008 AN: 41446

American (AMR) AF: 0.175 AC: 2667 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 578 AN: 3468

East Asian (EAS) AF: 0.0519 AC: 269 AN: 5184

South Asian (SAS) AF: 0.0885 AC: 427 AN: 4826

European-Finnish (FIN) AF: 0.215 AC: 2276 AN: 10590

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14823 AN: 67982

Other (OTH) AF: 0.181 AC: 382 AN: 2110

Alfa AF: 0.212 Hom.: 2670

Bravo AF: 0.226

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.58
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs238150; hg19: chr20-47851919;