Variant 20-21333776-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_012255.5(XRN2):c.1006G>A(p.Val336Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,614,082 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 14 hom. )

Consequence

XRN2
NM_012255.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.97

Variant links:

Genes affected

XRN2 (HGNC:12836): (5'-3' exoribonuclease 2) This gene encodes a 5'-3' exonuclease that promotes transcription termination at cotranscriptional cleavage sites. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

XRN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010895699).

BP6

Variant 20-21333776-G-A is Benign according to our data. Variant chr20-21333776-G-A is described in ClinVar as [Benign]. Clinvar id is 724653.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
XRN2	NM_012255.5 linkuse as main transcript	c.1006G>A	p.Val336Ile	missense_variant	11/30	ENST00000377191.5	NP_036387.2
XRN2	NM_001317960.1 linkuse as main transcript	c.1240G>A	p.Val414Ile	missense_variant	11/30		NP_001304889.1
XRN2	XM_017027722.2 linkuse as main transcript	c.1240G>A	p.Val414Ile	missense_variant	11/17		XP_016883211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRN2	ENST00000377191.5 linkuse as main transcript	c.1006G>A	p.Val336Ile	missense_variant	11/30	1	NM_012255.5	ENSP00000366396	P1	Q9H0D6-1

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

341

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00181

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00216

AC:

542

AN:

251184

Hom.:

AF XY:

0.00216

AC XY:

293

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.00211

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00203

AC:

2968

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1440

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00224

AC:

341

AN:

152238

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.00181

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00128

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00202

AC:

245

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00175

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.014

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.97

REVEL

Benign

0.25

Sift

Benign

0.10

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.70

MVP

0.40

MPC

0.91

ClinPred

0.036

GERP RS

5.7

Varity_R

0.16

gMVP

0.60

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