20-49225123-G-T

Variant names:

• chr20-49225123-G-T
• rs11553387
• NM_017895.8:c.524G>T

Variant summary

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

The NM_017895.8(DDX27):​c.524G>T​(p.Gly175Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,612,734 control chromosomes in the GnomAD database, including 33,994 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (2961 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31033 hom.)
• Consequence: DDX27 NM_017895.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.49
• Publications: 33 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 (MetaRNN=0.0014153719).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX27	NM_017895.8	c.524G>T	p.Gly175Val	missense_variant	Exon 6 of 21	ENST00000618172.5	NP_060365.8
DDX27	NM_001348187.2	c.524G>T	p.Gly175Val	missense_variant	Exon 6 of 22		NP_001335116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX27	ENST00000618172.5	c.524G>T	p.Gly175Val	missense_variant	Exon 6 of 21	1	NM_017895.8	ENSP00000482680.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29684 AN: 151938 Hom.: 2960 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0858

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.174 AC: 43867 AN: 251472 AF XY: 0.171

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.0416

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.201 AC: 293482 AN: 1460678 Hom.: 31033 Cov.: 32 AF XY: 0.197 AC XY: 143085 AN XY: 726658

African (AFR) AF: 0.196 AC: 6550 AN: 33452

American (AMR) AF: 0.165 AC: 7386 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4387 AN: 26128

East Asian (EAS) AF: 0.0664 AC: 2635 AN: 39696

South Asian (SAS) AF: 0.0830 AC: 7158 AN: 86238

European-Finnish (FIN) AF: 0.212 AC: 11306 AN: 53412

Middle Eastern (MID) AF: 0.138 AC: 796 AN: 5768

European-Non Finnish (NFE) AF: 0.218 AC: 242148 AN: 1110910

Other (OTH) AF: 0.184 AC: 11116 AN: 60354

GnomAD4 genome AF: 0.195 AC: 29700 AN: 152056 Hom.: 2961 Cov.: 32 AF XY: 0.190 AC XY: 14150 AN XY: 74342

African (AFR) AF: 0.200 AC: 8284 AN: 41456

American (AMR) AF: 0.160 AC: 2441 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3470

East Asian (EAS) AF: 0.0521 AC: 270 AN: 5182

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4820

European-Finnish (FIN) AF: 0.215 AC: 2273 AN: 10584

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14743 AN: 67968

Other (OTH) AF: 0.160 AC: 336 AN: 2104

Alfa AF: 0.204 Hom.: 12902

Bravo AF: 0.189

TwinsUK AF: 0.217 AC: 803

ALSPAC AF: 0.217 AC: 835

ESP6500AA AF: 0.187 AC: 826

ESP6500EA AF: 0.223 AC: 1918

ExAC AF: 0.176 AC: 21375

Asia WGS AF: 0.0920 AC: 320 AN: 3478

EpiCase AF: 0.205

EpiControl AF: 0.200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-0.096
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;.;D
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.9	L;L;.
PhyloP100		3.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.0	.;N;.
REVEL	Benign	0.0
Sift	Pathogenic	0.0	.;T;.
Sift4G	Benign	0.27	T;T;T
Vest4		0.11
ClinPred		0.0081	T
GERP RS		5.2
PromoterAI		-0.0084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.22
gMVP		0.24
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.010		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: rs11553387; hg19: chr20-47841660; COSMIC: COSV65629728;