Genetic Variant USP17L2:p.Leu363Leu (chr8-12137674-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_201402.3(USP17L2):c.1087C>T(p.Leu363Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,532,466 control chromosomes in the GnomAD database, including 351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 19 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 332 hom. )

Consequence

USP17L2
NM_201402.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.779

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 8-12137674-G-A is Benign according to our data. Variant chr8-12137674-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658424.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.779 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L2	NM_201402.3 link	c.1087C>T	p.Leu363Leu	synonymous_variant	Exon 1 of 1	ENST00000333796.4	NP_958804.2	Q6R6M4
FAM66D	NR_027425.1 link	n.609-7749G>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.1087C>T	p.Leu363Leu	synonymous_variant	Exon 1 of 1	6	NM_201402.3	ENSP00000333329.3		Q6R6M4

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

189

AN:

140810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000562

Gnomad AMI

AF:

0.00598

Gnomad AMR

AF:

0.000577

Gnomad ASJ

AF:

0.00179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00156

AC:

366

AN:

234182

Hom.:

AF XY:

0.00165

AC XY:

209

AN XY:

126870

show subpopulations

Gnomad AFR exome

AF:

0.000631

Gnomad AMR exome

AF:

0.000524

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00218

Gnomad OTH exome

AF:

0.00156

GnomAD4 exome

AF:

0.00264

AC:

3672

AN:

1391564

Hom.:

332

Cov.:

AF XY:

0.00263

AC XY:

1821

AN XY:

691336

show subpopulations

Gnomad4 AFR exome

AF:

0.000226

Gnomad4 AMR exome

AF:

0.000547

Gnomad4 ASJ exome

AF:

0.00204

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00272

Gnomad4 FIN exome

AF:

0.0000391

Gnomad4 NFE exome

AF:

0.00303

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00134

AC:

189

AN:

140902

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

68470

show subpopulations

Gnomad4 AFR

AF:

0.000561

Gnomad4 AMR

AF:

0.000577

Gnomad4 ASJ

AF:

0.00179

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00102

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

USP17L2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.0

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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