dbSNP rs201233406: USP17L2:p.Gln296Leu (chr8-12137874-T-A) – 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.887A>T(p.Gln296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,526,540 control chromosomes in the GnomAD database, including 309 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 0.0017 ( 31 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 278 hom. )

Consequence

USP17L2
NM_201402.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.688

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=0.018048763).

BP6

Variant 8-12137874-T-A is Benign according to our data. Variant chr8-12137874-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658425.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L2	NM_201402.3 link	c.887A>T	p.Gln296Leu	missense_variant	Exon 1 of 1	ENST00000333796.4	NP_958804.2	Q6R6M4
FAM66D	NR_027425.1 link	n.609-7549T>A		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP17L2	ENST00000333796.4 link	c.887A>T	p.Gln296Leu	missense_variant	Exon 1 of 1	6	NM_201402.3	ENSP00000333329.3		Q6R6M4

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

245

AN:

140908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000561

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000648

Gnomad ASJ

AF:

0.00329

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000203

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00305

Gnomad OTH

AF:

0.00205

GnomAD3 exomes

AF:

0.00151

AC:

334

AN:

221844

Hom.:

AF XY:

0.00151

AC XY:

183

AN XY:

121006

show subpopulations

Gnomad AFR exome

AF:

0.000243

Gnomad AMR exome

AF:

0.000727

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000100

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.000892

GnomAD4 exome

AF:

0.00195

AC:

2706

AN:

1385538

Hom.:

278

Cov.:

AF XY:

0.00188

AC XY:

1296

AN XY:

689462

show subpopulations

Gnomad4 AFR exome

AF:

0.000254

Gnomad4 AMR exome

AF:

0.000543

Gnomad4 ASJ exome

AF:

0.00371

Gnomad4 EAS exome

AF:

0.0000288

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000119

Gnomad4 NFE exome

AF:

0.00234

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.00174

AC:

245

AN:

141002

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

111

AN XY:

68460

show subpopulations

Gnomad4 AFR

AF:

0.000560

Gnomad4 AMR

AF:

0.000647

Gnomad4 ASJ

AF:

0.00329

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000203

Gnomad4 NFE

AF:

0.00305

Gnomad4 OTH

AF:

0.00203

Alfa

AF:

0.00277

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00208

AC:

ExAC

AF:

0.00162

AC:

180

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FAM66D: BS2; USP17L2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

5.4

DANN

Benign

0.86

DEOGEN2

Benign

0.0051

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.78

M_CAP

Benign

0.0013

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.035

Sift

Benign

0.047

Sift4G

Benign

0.12

Polyphen

0.47

Vest4

0.15

MVP

0.20

MPC

0.96

ClinPred

0.092

GERP RS

-1.5

Varity_R

0.11

gMVP

0.034

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