20-21338339-A-C

Variant names:

• chr20-21338339-A-C
• rs10485627
• NM_012255.5:c.1234-705A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012255.5(XRN2):​c.1234-705A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,204 control chromosomes in the GnomAD database, including 1,298 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 0.078 (1298 hom., cov: 32)
• Consequence: XRN2 NM_012255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012255.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRN2	NM_012255.5	MANE Select	c.1234-705A>C		intron	N/A	NP_036387.2
	XRN2	NM_001317960.1		c.1468-705A>C		intron	N/A	NP_001304889.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRN2	ENST00000377191.5	TSL:1 MANE Select	c.1234-705A>C		intron	N/A	ENSP00000366396.3

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11851 AN: 152086 Hom.: 1292 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0965

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0646

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0780 AC: 11877 AN: 152204 Hom.: 1298 Cov.: 32 AF XY: 0.0767 AC XY: 5711 AN XY: 74430

African (AFR) AF: 0.231 AC: 9594 AN: 41476

American (AMR) AF: 0.0278 AC: 425 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1164 AN: 5174

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 68024

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0389 Hom.: 1062

Bravo AF: 0.0859

Asia WGS AF: 0.134 AC: 465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.75
PhyloP100		0.11
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

Other links and lift over

dbSNP: rs10485627; hg19: chr20-21318977;