Genetic Variant USP17L2:p.Val500Met (chr8-12137263-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_201402.3(USP17L2):c.1498G>A(p.Val500Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,528,980 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 30 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 68 hom. )

Consequence

USP17L2
NM_201402.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005227953).

BP6

Variant 8-12137263-C-T is Benign according to our data. Variant chr8-12137263-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658423.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L2	NM_201402.3 link	c.1498G>A	p.Val500Met	missense_variant	Exon 1 of 1	ENST00000333796.4	NP_958804.2	Q6R6M4
FAM66D	NR_027425.1 link	n.609-8160C>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.1498G>A	p.Val500Met	missense_variant	Exon 1 of 1	6	NM_201402.3	ENSP00000333329.3		Q6R6M4

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

386

AN:

140148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00828

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00102

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000468

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000910

Gnomad OTH

AF:

0.00207

GnomAD3 exomes

AF:

0.000867

AC:

199

AN:

229644

Hom.:

AF XY:

0.000685

AC XY:

AN XY:

125468

show subpopulations

Gnomad AFR exome

AF:

0.00756

Gnomad AMR exome

AF:

0.000340

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00195

Gnomad SAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.000194

Gnomad NFE exome

AF:

0.000426

Gnomad OTH exome

AF:

0.000874

GnomAD4 exome

AF:

0.00108

AC:

1496

AN:

1388740

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

701

AN XY:

689806

show subpopulations

Gnomad4 AFR exome

AF:

0.00789

Gnomad4 AMR exome

AF:

0.000571

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000976

Gnomad4 SAS exome

AF:

0.0000388

Gnomad4 FIN exome

AF:

0.000140

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00276

AC:

387

AN:

140240

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

160

AN XY:

68040

show subpopulations

Gnomad4 AFR

AF:

0.00826

Gnomad4 AMR

AF:

0.00102

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000704

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000910

Gnomad4 OTH

AF:

0.00205

Alfa

AF:

0.00158

Hom.:

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00117

AC:

ExAC

AF:

0.00114

AC:

127

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

USP17L2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.1

DANN

Benign

0.39

DEOGEN2

Benign

0.00092

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.39

M_CAP

Benign

0.0012

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.49

REVEL

Benign

0.012

Sift

Benign

0.50

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.061

MVP

0.13

MPC

0.37

ClinPred

0.00073

GERP RS

-0.84

Varity_R

0.044

gMVP

0.019

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