Genetic Variant NM_201402.3:c.148G>A (chr8-12138613-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.148G>A(p.Asp50Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,530,522 control chromosomes in the GnomAD database, including 17 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 0.00020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 16 hom. )

Consequence

USP17L2
NM_201402.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.632

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=0.03296557).

BP6

Variant 8-12138613-C-T is Benign according to our data. Variant chr8-12138613-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658429.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L2	NM_201402.3 link	c.148G>A	p.Asp50Asn	missense_variant	Exon 1 of 1	ENST00000333796.4	NP_958804.2	Q6R6M4
FAM66D	NR_027425.1 link	n.609-6810C>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.148G>A	p.Asp50Asn	missense_variant	Exon 1 of 1	6	NM_201402.3	ENSP00000333329.3		Q6R6M4

Frequencies

GnomAD3 genomes

AF:

0.000200

AC:

AN:

140156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00362

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00158

GnomAD3 exomes

AF:

0.000301

AC:

AN:

229146

Hom.:

AF XY:

0.000335

AC XY:

AN XY:

125422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000699

GnomAD4 exome

AF:

0.000225

AC:

313

AN:

1390274

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

165

AN XY:

690568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000309

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000362

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.000526

GnomAD4 genome

AF:

0.000200

AC:

AN:

140248

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

AN XY:

68132

show subpopulations

Gnomad4 AFR

AF:

0.0000537

Gnomad4 AMR

AF:

0.000145

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00156

Alfa

AF:

0.000491

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000368

AC:

ExAC

AF:

0.000272

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 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

0.076

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.040

DANN

Benign

0.62

DEOGEN2

Benign

0.0026

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.66

M_CAP

Benign

0.0010

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.060

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.32

REVEL

Benign

0.017

Sift

Benign

0.44

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.095

MVP

0.10

MPC

0.36

ClinPred

0.012

GERP RS

-0.72

Varity_R

0.040

gMVP

0.041

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