Variant 14-90288671-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017970.4(NRDE2):c.2704C>T(p.Arg902Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,614,142 control chromosomes in the GnomAD database, including 19 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 18 hom. )

Consequence

NRDE2
NM_017970.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

NRDE2 (HGNC:20186): (NRDE-2, necessary for RNA interference, domain containing) Involved in several processes, including RNA splicing; negative regulation of RNA catabolic process; and positive regulation of RNA export from nucleus. Located in nuclear speck and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

NRDE2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013383478).

BP6

Variant 14-90288671-G-A is Benign according to our data. Variant chr14-90288671-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644448.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRDE2	NM_017970.4 linkuse as main transcript	c.2704C>T	p.Arg902Cys	missense_variant	11/14	ENST00000354366.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NRDE2	ENST00000354366.8 linkuse as main transcript	c.2704C>T	p.Arg902Cys	missense_variant	11/14	1	NM_017970.4	P1
NRDE2	ENST00000553409.5 linkuse as main transcript	c.*2229C>T		3_prime_UTR_variant, NMD_transcript_variant	9/12	1
NRDE2	ENST00000556189.5 linkuse as main transcript	c.*1182C>T		3_prime_UTR_variant, NMD_transcript_variant	7/10	1
NRDE2	ENST00000555903.1 linkuse as main transcript	n.215C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

266

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00219

AC:

551

AN:

251334

Hom.:

AF XY:

0.00259

AC XY:

352

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00434

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00237

AC:

3458

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00254

AC XY:

1844

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00458

Gnomad4 FIN exome

AF:

0.000918

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.00175

AC:

266

AN:

152314

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00228

AC:

277

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00322

EpiControl

AF:

0.00356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

NRDE2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

Cadd

Benign

Dann

Benign

0.75

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.72

M_CAP

Benign

0.0038

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.21

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.16

REVEL

Benign

0.030

Sift

Benign

0.19

Sift4G

Benign

0.22

Polyphen

0.0020

Vest4

0.18

MVP

0.35

MPC

0.086

ClinPred

0.010

GERP RS

1.5

Varity_R

0.039

gMVP

0.19

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

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