10-12009817-G-A

Position:

• chr10-12009817-G-A

Variant summary

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

The NM_015542.4(UPF2):​c.1306+4207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,092 control chromosomes in the GnomAD database, including 13,086 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 0.38 (13086 hom., cov: 31)
• Consequence: UPF2 NM_015542.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

Genes affected

UPF2 (HGNC:17854): (UPF2 regulator of nonsense mediated mRNA decay) This gene encodes a protein that is part of a post-splicing multiprotein complex involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in the perinuclear area. It interacts with translation release factors and the proteins that are functional homologs of yeast Upf1p and Upf3p. Two splice variants have been found for this gene; both variants encode the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPF2	NM_015542.4	c.1306+4207C>T		intron_variant		ENST00000357604.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPF2	ENST00000357604.10	c.1306+4207C>T		intron_variant		1	NM_015542.4	P1
UPF2	ENST00000356352.6	c.1306+4207C>T		intron_variant		1		P1
UPF2	ENST00000397053.6	c.1306+4207C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57426 AN: 151974 Hom.: 13078 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.378 AC: 57448 AN: 152092 Hom.: 13086 Cov.: 31 AF XY: 0.379 AC XY: 28149 AN XY: 74364

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.409

Alfa AF: 0.473 Hom.: 17185

Bravo AF: 0.355

Asia WGS AF: 0.397 AC: 1382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.71

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: rs10795917; hg19: chr10-12051816;