rs2025811

Variant names:

• chr20-21354475-T-C
• rs2025811
• NM_012255.5:c.1937-314T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767

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]

ACMG classification

Verdict is Benign. Variant got -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
XRN2	NM_012255.5	c.1937-314T>C		intron_variant	Intron 20 of 29	ENST00000377191.5	NP_036387.2
XRN2	NM_001317960.1	c.2171-314T>C		intron_variant	Intron 20 of 29		NP_001304889.1
XRN2	XM_017027723.3	c.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
XRN2	ENST00000377191.5	c.1937-314T>C		intron_variant	Intron 20 of 29	1	NM_012255.5	ENSP00000366396.3

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135399 AN: 152106 Hom.: 60583 Cov.: 31

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

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.912

Alfa AF: 0.861 Hom.: 71739

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

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

Other links and lift over

dbSNP: rs2025811; hg19: chr20-21335113;