20-49234077-A-T

Variant names:

• chr20-49234077-A-T
• rs1079661
• NM_017895.8:c.1273+368A>T

Variant summary

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

The NM_001348187.2(DDX27):​c.1366+368A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 205,356 control chromosomes in the GnomAD database, including 22,770 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 0.45 (16495 hom., cov: 32)
  • Exomes 𝑓: 0.47 (6275 hom.)
• Consequence: DDX27 NM_001348187.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348187.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX27	NM_017895.8	MANE Select	c.1273+368A>T		intron	N/A	NP_060365.8
	DDX27	NM_001348187.2		c.1366+368A>T		intron	N/A	NP_001335116.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX27	ENST00000618172.5	TSL:1 MANE Select	c.1273+368A>T		intron	N/A	ENSP00000482680.1
	DDX27	ENST00000471144.1	TSL:1	n.240A>T		non_coding_transcript_exon	Exon 1 of 7
	DDX27	ENST00000484427.5	TSL:1	n.1743A>T		non_coding_transcript_exon	Exon 11 of 19

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67737 AN: 151914 Hom.: 16502 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.472 AC: 25171 AN: 53324 Hom.: 6275 Cov.: 0 AF XY: 0.481 AC XY: 13179 AN XY: 27386

African (AFR) AF: 0.207 AC: 682 AN: 3292

American (AMR) AF: 0.377 AC: 1623 AN: 4306

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 954 AN: 1692

East Asian (EAS) AF: 0.405 AC: 1882 AN: 4642

South Asian (SAS) AF: 0.436 AC: 1411 AN: 3236

European-Finnish (FIN) AF: 0.542 AC: 985 AN: 1816

Middle Eastern (MID) AF: 0.631 AC: 135 AN: 214

European-Non Finnish (NFE) AF: 0.515 AC: 16067 AN: 31196

Other (OTH) AF: 0.489 AC: 1432 AN: 2930

GnomAD4 genome AF: 0.445 AC: 67730 AN: 152032 Hom.: 16495 Cov.: 32 AF XY: 0.447 AC XY: 33243 AN XY: 74324

African (AFR) AF: 0.236 AC: 9797 AN: 41452

American (AMR) AF: 0.433 AC: 6607 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2166 AN: 3470

East Asian (EAS) AF: 0.453 AC: 2338 AN: 5160

South Asian (SAS) AF: 0.463 AC: 2234 AN: 4820

European-Finnish (FIN) AF: 0.577 AC: 6106 AN: 10578

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36850 AN: 67976

Other (OTH) AF: 0.489 AC: 1032 AN: 2112

Alfa AF: 0.492 Hom.: 2403

Bravo AF: 0.429

Asia WGS AF: 0.442 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.62
PhyloP100		0.071
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: rs1079661; hg19: chr20-47850614;