20-49219498-T-A

Position:

• chr20-49219498-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017895.8(DDX27):​c.50T>A​(p.Val17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DDX27 NM_017895.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.842

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]

DDX27 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX27	NM_017895.8	c.50T>A	p.Val17Glu	missense_variant	1/21	ENST00000618172.5	NP_060365.8
DDX27	NM_001348187.2	c.50T>A	p.Val17Glu	missense_variant	1/22		NP_001335116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX27	ENST00000618172.5	c.50T>A	p.Val17Glu	missense_variant	1/21	1	NM_017895.8	ENSP00000482680.1
DDX27	ENST00000484427.5	n.152T>A		non_coding_transcript_exon_variant	1/19	1
DDX27	ENST00000462328.2	n.50T>A		non_coding_transcript_exon_variant	1/7	5		ENSP00000481808.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.143T>A (p.V48E) alteration is located in exon 1 (coding exon 1) of the DDX27 gene. This alteration results from a T to A substitution at nucleotide position 143, causing the valine (V) at amino acid position 48 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.096
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.71	T;.;T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.1	.;N;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	.;D;.
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.59
MutPred		0.26		Gain of disorder (P = 0.0764);Gain of disorder (P = 0.0764);.;
MVP		0.92
MPC		0.33
ClinPred		0.84	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.54
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-47836035;