20-49225113-G-A

Position:

chr20-49225113-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.85

Variant links:

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 links:

DDX27 (HGNC:):

DDX27 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
DDX27	NM_017895.8 linkuse as main transcript	c.514G>A	p.Glu172Lys	missense_variant, splice_region_variant	6/21	ENST00000618172.5	NP_060365.8
DDX27	NM_001348187.2 linkuse as main transcript	c.514G>A	p.Glu172Lys	missense_variant, splice_region_variant	6/22		NP_001335116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX27	ENST00000618172.5 linkuse as main transcript	c.514G>A	p.Glu172Lys	missense_variant, splice_region_variant	6/21	1	NM_017895.8	ENSP00000482680.1		B7Z6D5

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1202

AN:

152180

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00163

AC XY:

221

AN XY:

135912

show subpopulations

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.:

Cov.:

AF XY:

0.000605

AC XY:

440

AN XY:

727154

show subpopulations

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.:

Cov.:

AF XY:

0.00798

AC XY:

594

AN XY:

74472

show subpopulations

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.:

Bravo

AF:

0.00930

ESP6500AA

AF:

0.0309

AC:

136

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00273

AC:

332

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

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

LIST_S2

Benign

0.68

T;.;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.3

L;L;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

.;N;.

REVEL

Benign

0.11

Sift

Benign

0.099

.;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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over