Variant chr10-11955340-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_015542.4(UPF2):c.2742G>A(p.Glu914=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000807 in 1,614,100 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 7 hom. )

Consequence

UPF2
NM_015542.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.428

Variant links:

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]

UPF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 10-11955340-C-T is Benign according to our data. Variant chr10-11955340-C-T is described in ClinVar as [Benign]. Clinvar id is 776497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.428 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000438 (640/1461860) while in subpopulation AFR AF= 0.0167 (560/33480). AF 95% confidence interval is 0.0156. There are 7 homozygotes in gnomad4_exome. There are 268 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UPF2	NM_015542.4 linkuse as main transcript	c.2742G>A	p.Glu914=	synonymous_variant	14/22	ENST00000357604.10
UPF2	NM_080599.3 linkuse as main transcript	c.2742G>A	p.Glu914=	synonymous_variant	14/22
UPF2	XM_047424986.1 linkuse as main transcript	c.2742G>A	p.Glu914=	synonymous_variant	14/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
UPF2	ENST00000357604.10 linkuse as main transcript	c.2742G>A	p.Glu914=	synonymous_variant	14/22	1	NM_015542.4	P1
UPF2	ENST00000356352.6 linkuse as main transcript	c.2742G>A	p.Glu914=	synonymous_variant	13/21	1		P1
UPF2	ENST00000397053.6 linkuse as main transcript	c.2742G>A	p.Glu914=	synonymous_variant	14/22	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00436

AC:

664

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00113

AC:

285

AN:

251364

Hom.:

AF XY:

0.000817

AC XY:

111

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000438

AC:

640

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

268

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0167

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.00435

AC:

663

AN:

152240

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

301

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00293

Hom.:

Bravo

AF:

0.00495

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

4.7

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over