rs7899260

chr10-12009575-A-G

Variant summary

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

The NM_015542.4(UPF2):c.1306+4449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 152,296 control chromosomes in the GnomAD database, including 365 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 0.063 (365 hom., cov: 32)
• Consequence: UPF2 NM_015542.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPF2	NM_015542.4	c.1306+4449T>C		intron_variant		ENST00000357604.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPF2	ENST00000357604.10	c.1306+4449T>C		intron_variant		1	NM_015542.4	P1
UPF2	ENST00000356352.6	c.1306+4449T>C		intron_variant		1		P1
UPF2	ENST00000397053.6	c.1306+4449T>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9520 AN: 152178 Hom.: 365 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0559

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0625 AC: 9524 AN: 152296 Hom.: 365 Cov.: 32 AF XY: 0.0609 AC XY: 4539 AN XY: 74476

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0727

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0468

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.0897

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0847 Hom.: 808

Bravo AF: 0.0619

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.3
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: rs7899260; hg19: chr10-12051574;