rs11257462

Positions:

• chr10-11978982-C-A

Variant summary

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

The NM_015542.4(UPF2):​c.1953+75G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,204,266 control chromosomes in the GnomAD database, including 11,636 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 0.13 (1381 hom., cov: 32)
  • Exomes 𝑓: 0.13 (10255 hom.)
• Consequence: UPF2 NM_015542.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPF2	NM_015542.4	c.1953+75G>T		intron_variant		ENST00000357604.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPF2	ENST00000357604.10	c.1953+75G>T		intron_variant		1	NM_015542.4	P1
UPF2	ENST00000356352.6	c.1953+75G>T		intron_variant		1		P1
UPF2	ENST00000397053.6	c.1953+75G>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19832 AN: 152064 Hom.: 1376 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.131 AC: 137711 AN: 1052084 Hom.: 10255 AF XY: 0.134 AC XY: 71693 AN XY: 533632

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.0746

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.131 AC: 19860 AN: 152182 Hom.: 1381 Cov.: 32 AF XY: 0.133 AC XY: 9880 AN XY: 74406

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.0770

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.150

Alfa AF: 0.131 Hom.: 498

Bravo AF: 0.142

Asia WGS AF: 0.208 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.1
DANN	Benign	0.55

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: rs11257462; hg19: chr10-12020981;