chr10-11978982-C-A

Variant names:

• chr10-11978982-C-A
• rs11257462
• NM_015542.4:c.1953+75G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UPF2	NM_015542.4	c.1953+75G>T		intron_variant	Intron 9 of 21	ENST00000357604.10	NP_056357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPF2	ENST00000357604.10	c.1953+75G>T		intron_variant	Intron 9 of 21	1	NM_015542.4	ENSP00000350221.5
UPF2	ENST00000356352.6	c.1953+75G>T		intron_variant	Intron 8 of 20	1		ENSP00000348708.2
UPF2	ENST00000397053.6	c.1953+75G>T		intron_variant	Intron 9 of 21	5		ENSP00000380244.2

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

African (AFR) AF: 0.141 AC: 3327 AN: 23578

American (AMR) AF: 0.232 AC: 8432 AN: 36304

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 4369 AN: 21660

East Asian (EAS) AF: 0.107 AC: 3728 AN: 34680

South Asian (SAS) AF: 0.255 AC: 17542 AN: 68686

European-Finnish (FIN) AF: 0.0746 AC: 3713 AN: 49788

Middle Eastern (MID) AF: 0.178 AC: 861 AN: 4832

European-Non Finnish (NFE) AF: 0.116 AC: 89177 AN: 766438

Other (OTH) AF: 0.142 AC: 6562 AN: 46118

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

African (AFR) AF: 0.132 AC: 5460 AN: 41502

American (AMR) AF: 0.187 AC: 2850 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 681 AN: 3470

East Asian (EAS) AF: 0.125 AC: 651 AN: 5190

South Asian (SAS) AF: 0.255 AC: 1233 AN: 4828

European-Finnish (FIN) AF: 0.0770 AC: 816 AN: 10596

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7603 AN: 68002

Other (OTH) AF: 0.150 AC: 317 AN: 2114

Alfa AF: 0.132 Hom.: 885

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
PhyloP100		-0.78
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: rs11257462; hg19: chr10-12020981;