20-49223391-A-G

Position:

• chr20-49223391-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017895.8(DDX27):​c.424A>G​(p.Thr142Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DDX27 NM_017895.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062397182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX27	NM_017895.8	c.424A>G	p.Thr142Ala	missense_variant	4/21	ENST00000618172.5
DDX27	NM_001348187.2	c.424A>G	p.Thr142Ala	missense_variant	4/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX27	ENST00000618172.5	c.424A>G	p.Thr142Ala	missense_variant	4/21	1	NM_017895.8	P1
DDX27	ENST00000484427.5	n.526A>G		non_coding_transcript_exon_variant	4/19	1
DDX27	ENST00000462328.2	c.424A>G	p.Thr142Ala	missense_variant, NMD_transcript_variant	4/7	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461306 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726950

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.51
DEOGEN2	Benign	0.0089	T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.60	T;.;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.0	L;L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.66	T;T;T
Polyphen		0.013	B;B;.
Vest4		0.087
MutPred		0.14		Loss of phosphorylation at T173 (P = 0.0126);Loss of phosphorylation at T173 (P = 0.0126);.;
MVP		0.18
MPC		0.16
ClinPred		0.060	T
GERP RS		2.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.031
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs1390764784; hg19: chr20-47839928;