rs2025811

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012255.5(XRN2):​c.1937-314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,224 control chromosomes in the GnomAD database, including 60,643 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.89 ( 60643 hom., cov: 31)

Consequence

XRN2
NM_012255.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.767

Publications

7 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
XRN2NM_012255.5 linkc.1937-314T>C intron_variant Intron 20 of 29 ENST00000377191.5 NP_036387.2 Q9H0D6-1
XRN2NM_001317960.1 linkc.2171-314T>C intron_variant Intron 20 of 29 NP_001304889.1 Q9H0D6B4DZC3
XRN2XM_017027723.3 linkc.665-314T>C intron_variant Intron 8 of 17 XP_016883212.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
XRN2ENST00000377191.5 linkc.1937-314T>C intron_variant Intron 20 of 29 1 NM_012255.5 ENSP00000366396.3 Q9H0D6-1

Frequencies

GnomAD3 genomes
AF:
0.890
AC:
135399
AN:
152106
Hom.:
60583
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.971
Gnomad AMI
AF:
0.826
Gnomad AMR
AF:
0.878
Gnomad ASJ
AF:
0.954
Gnomad EAS
AF:
0.996
Gnomad SAS
AF:
0.923
Gnomad FIN
AF:
0.809
Gnomad MID
AF:
0.946
Gnomad NFE
AF:
0.843
Gnomad OTH
AF:
0.910
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.890
AC:
135518
AN:
152224
Hom.:
60643
Cov.:
31
AF XY:
0.892
AC XY:
66386
AN XY:
74434
show subpopulations
African (AFR)
AF:
0.971
AC:
40365
AN:
41556
American (AMR)
AF:
0.878
AC:
13417
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.954
AC:
3310
AN:
3470
East Asian (EAS)
AF:
0.996
AC:
5169
AN:
5188
South Asian (SAS)
AF:
0.923
AC:
4441
AN:
4814
European-Finnish (FIN)
AF:
0.809
AC:
8561
AN:
10584
Middle Eastern (MID)
AF:
0.952
AC:
280
AN:
294
European-Non Finnish (NFE)
AF:
0.843
AC:
57296
AN:
68006
Other (OTH)
AF:
0.912
AC:
1927
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
714
1429
2143
2858
3572
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
900
1800
2700
3600
4500
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.862
Hom.:
82131
Bravo
AF:
0.897
Asia WGS
AF:
0.962
AC:
3341
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.89
DANN
Benign
0.43
PhyloP100
-0.77
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2025811; hg19: chr20-21335113; API