Variant 10-11955227-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015542.4(UPF2):c.2850+5A>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,579,360 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 111 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 95 hom. )

Consequence

UPF2
NM_015542.4 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.00005087

Clinical Significance

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

Conservation

PhyloP100: -0.134

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 10-11955227-T-C is Benign according to our data. Variant chr10-11955227-T-C is described in ClinVar as [Benign]. Clinvar id is 790079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
UPF2	NM_015542.4 linkuse as main transcript	c.2850+5A>G	splice_donor_5th_base_variant, intron_variant	ENST00000357604.10
UPF2	NM_080599.3 linkuse as main transcript	c.2850+5A>G	splice_donor_5th_base_variant, intron_variant
UPF2	XM_047424986.1 linkuse as main transcript	c.2850+5A>G	splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
UPF2	ENST00000357604.10 linkuse as main transcript	c.2850+5A>G	splice_donor_5th_base_variant, intron_variant	1	NM_015542.4	P1
UPF2	ENST00000356352.6 linkuse as main transcript	c.2850+5A>G	splice_donor_5th_base_variant, intron_variant	1		P1
UPF2	ENST00000397053.6 linkuse as main transcript	c.2850+5A>G	splice_donor_5th_base_variant, intron_variant	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3342

AN:

152182

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00664

AC:

1562

AN:

235332

Hom.:

AF XY:

0.00503

AC XY:

639

AN XY:

127136

show subpopulations

Gnomad AFR exome

AF:

0.0707

Gnomad AMR exome

AF:

0.00518

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000152

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000560

Gnomad OTH exome

AF:

0.00527

GnomAD4 exome

AF:

0.00273

AC:

3902

AN:

1427060

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1735

AN XY:

705378

show subpopulations

Gnomad4 AFR exome

AF:

0.0722

Gnomad4 AMR exome

AF:

0.00593

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000392

Gnomad4 OTH exome

AF:

0.00609

GnomAD4 genome

AF:

0.0220

AC:

3349

AN:

152300

Hom.:

111

Cov.:

AF XY:

0.0221

AC XY:

1643

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0726

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.0299

Hom.:

864

Bravo

AF:

0.0251

Asia WGS

AF:

0.00433

AC:

AN:

3478

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.0

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.010

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

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