20-49225113-G-A

Position:

• chr20-49225113-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017895.8(DDX27):​c.514G>A​(p.Glu172Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00141 in 1,613,930 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (21 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (9 hom.)
• Consequence: DDX27 NM_017895.8 missense, splice_region
• Scores: Splicing: ADA: 0.9997
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.85

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 20-49225113-G-A is Benign according to our data. Variant chr20-49225113-G-A is described in ClinVar as [Benign]. Clinvar id is 710156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00791 (1204/152298) while in subpopulation AFR AF= 0.0268 (1113/41574). AF 95% confidence interval is 0.0255. There are 21 homozygotes in gnomad4. There are 594 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX27	NM_017895.8	c.514G>A	p.Glu172Lys	missense_variant, splice_region_variant	6/21	ENST00000618172.5
DDX27	NM_001348187.2	c.514G>A	p.Glu172Lys	missense_variant, splice_region_variant	6/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX27	ENST00000618172.5	c.514G>A	p.Glu172Lys	missense_variant, splice_region_variant	6/21	1	NM_017895.8	P1
DDX27	ENST00000484427.5	n.616G>A		splice_region_variant, non_coding_transcript_exon_variant	6/19	1
DDX27	ENST00000493252.2	c.40G>A	p.Glu14Lys	missense_variant, splice_region_variant	2/8	3
DDX27	ENST00000462328.2	c.*174G>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	6/7	5

Frequencies

GnomAD3 genomes AF: 0.00790 AC: 1202 AN: 152180 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00209 AC: 525 AN: 251470 Hom.: 6 AF XY: 0.00163 AC XY: 221 AN XY: 135912

Gnomad AFR exome AF: 0.0283

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000738 AC: 1078 AN: 1461632 Hom.: 9 Cov.: 30 AF XY: 0.000605 AC XY: 440 AN XY: 727154

Gnomad4 AFR exome AF: 0.0266

Gnomad4 AMR exome AF: 0.00159

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome AF: 0.00791 AC: 1204 AN: 152298 Hom.: 21 Cov.: 32 AF XY: 0.00798 AC XY: 594 AN XY: 74472

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.000982 Hom.: 2

Bravo AF: 0.00930

ESP6500AA AF: 0.0309 AC: 136

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00273 AC: 332

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0098	T;T;T
Eigen	Benign	-0.067
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.68	T;.;T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.3	L;L;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.058	B;B;.
Vest4		0.39
MVP		0.27
MPC		0.18
ClinPred		0.0087	T
GERP RS		5.9
Varity_R		0.14
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.90
SpliceAI score (max)		0.16		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: rs151239397; hg19: chr20-47841650; COSMIC: COSV99057078;