Variant chr10-11943060-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015542.4(UPF2):c.3279+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,599,592 control chromosomes in the GnomAD database, including 3 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

UPF2
NM_015542.4 splice_region, intron

Scores

Splicing: ADA: 0.00009097

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-11943060-G-A is Benign according to our data. Variant chr10-11943060-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 714446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 245 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
UPF2	NM_015542.4 linkuse as main transcript	c.3279+4C>T	splice_region_variant, intron_variant	ENST00000357604.10	NP_056357.1	Q9HAU5
UPF2	NM_080599.3 linkuse as main transcript	c.3279+4C>T	splice_region_variant, intron_variant		NP_542166.1	Q9HAU5
UPF2	XM_047424986.1 linkuse as main transcript	c.3279+4C>T	splice_region_variant, intron_variant		XP_047280942.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
UPF2	ENST00000357604.10 linkuse as main transcript	c.3279+4C>T	splice_region_variant, intron_variant	1	NM_015542.4	ENSP00000350221.5	Q9HAU5
UPF2	ENST00000356352.6 linkuse as main transcript	c.3279+4C>T	splice_region_variant, intron_variant	1		ENSP00000348708.2	Q9HAU5
UPF2	ENST00000397053.6 linkuse as main transcript	c.3279+4C>T	splice_region_variant, intron_variant	5		ENSP00000380244.2	Q9HAU5

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

244

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00541

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000581

AC:

144

AN:

248034

Hom.:

AF XY:

0.000455

AC XY:

AN XY:

134134

show subpopulations

Gnomad AFR exome

AF:

0.00648

Gnomad AMR exome

AF:

0.000650

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000401

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000216

AC:

312

AN:

1447472

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

137

AN XY:

721024

show subpopulations

Gnomad4 AFR exome

AF:

0.00540

Gnomad4 AMR exome

AF:

0.000657

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000363

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000454

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.00161

AC:

245

AN:

152120

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

115

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00542

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000938

Hom.:

Bravo

AF:

0.00200

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.28

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.13

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