Genetic Variant USP17L2:p.Pro262Pro (chr8-12137975-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_201402.3(USP17L2):c.786G>A(p.Pro262Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,475,284 control chromosomes in the GnomAD database, including 131,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 11091 hom., cov: 32)

Exomes 𝑓: 0.45 ( 120118 hom. )

Consequence

USP17L2
NM_201402.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.45

Variant links:

Genes affected

USP17L2 (HGNC:34434): (ubiquitin specific peptidase 17 like family member 2) DUB3 is a member of the ubiquitin processing protease (UBP) subfamily of deubiquitinating enzymes. See USP1 (MIM 603478) for background information.[supplied by OMIM, Mar 2008]

USP17L2 links:

FAM66D (HGNC:24159): (family with sequence similarity 66 member D)

FAM66D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 8-12137975-C-T is Benign according to our data. Variant chr8-12137975-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 768228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L2	NM_201402.3 link	c.786G>A	p.Pro262Pro	synonymous_variant	Exon 1 of 1	ENST00000333796.4	NP_958804.2	Q6R6M4
FAM66D	NR_027425.1 link	n.609-7448C>T		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP17L2	ENST00000333796.4 link	c.786G>A	p.Pro262Pro	synonymous_variant	Exon 1 of 1	6	NM_201402.3	ENSP00000333329.3		Q6R6M4

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

56611

AN:

135626

Hom.:

11088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.368

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.524

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.449

GnomAD3 exomes

AF:

0.457

AC:

96461

AN:

210994

Hom.:

21659

AF XY:

0.452

AC XY:

52149

AN XY:

115356

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.496

Gnomad EAS exome

AF:

0.377

Gnomad SAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.506

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.446

AC:

597654

AN:

1339572

Hom.:

120118

Cov.:

AF XY:

0.445

AC XY:

297283

AN XY:

667304

show subpopulations

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.558

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.377

Gnomad4 SAS exome

AF:

0.414

Gnomad4 FIN exome

AF:

0.511

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.417

AC:

56634

AN:

135712

Hom.:

11091

Cov.:

AF XY:

0.421

AC XY:

27624

AN XY:

65690

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.524

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.352

Hom.:

1175

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

4.9

DANN

Benign

0.66

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

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