chr20-49234077-A-G

Variant names:

• chr20-49234077-A-G
• rs1079661
• ENST00000471144.1:n.240A>G

Variant summary

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

The ENST00000471144.1(DDX27):​n.240A>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 0.0000187 in 53,566 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: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: DDX27 ENST00000471144.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 0 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: 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=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX27	NM_017895.8	c.1273+368A>G		intron_variant	Intron 11 of 20	ENST00000618172.5	NP_060365.8
DDX27	NM_001348187.2	c.1366+368A>G		intron_variant	Intron 12 of 21		NP_001335116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX27	ENST00000471144.1	n.240A>G		non_coding_transcript_exon_variant	Exon 1 of 7	1
DDX27	ENST00000484427.5	n.1743A>G		non_coding_transcript_exon_variant	Exon 11 of 19	1
DDX27	ENST00000618172.5	c.1273+368A>G		intron_variant	Intron 11 of 20	1	NM_017895.8	ENSP00000482680.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000187 AC: 1 AN: 53566 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27510

⚠️ 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: 3304

American (AMR) AF: 0.00 AC: 0 AN: 4326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1706

East Asian (EAS) AF: 0.00 AC: 0 AN: 4654

South Asian (SAS) AF: 0.00 AC: 0 AN: 3250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.0000319 AC: 1 AN: 31342

Other (OTH) AF: 0.00 AC: 0 AN: 2942

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.32
PhyloP100		0.071

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;