dbSNP rs199985479: USP17L2:p.Asp50Asn (chr8-12138613-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/22 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

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2658429.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201402.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L2	NM_201402.3	MANE Select	c.148G>A	p.Asp50Asn	missense	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-6810C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP17L2	ENST00000333796.4	TSL:6 MANE Select	c.148G>A	p.Asp50Asn	missense	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
FAM66D	ENST00000434078.3	TSL:5	n.545-7026C>T		intron	N/A
FAM66D	ENST00000653269.1		n.706-6810C>T		intron	N/A

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

GnomAD2 exomes

AF:

0.000301

AC:

AN:

229146

AF XY:

0.000335

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30838

American (AMR)

AF:

0.000309

AC:

AN:

42048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25072

East Asian (EAS)

AF:

0.00

AC:

AN:

34180

South Asian (SAS)

AF:

0.000362

AC:

AN:

77284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50052

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

3820

European-Non Finnish (NFE)

AF:

0.000214

AC:

229

AN:

1069952

Other (OTH)

AF:

0.000526

AC:

AN:

57028

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.346

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000200

AC:

AN:

140248

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

AN XY:

68132

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000537

AC:

AN:

37214

American (AMR)

AF:

0.000145

AC:

AN:

13818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3338

East Asian (EAS)

AF:

0.00

AC:

AN:

4278

South Asian (SAS)

AF:

0.00

AC:

AN:

4002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9806

Middle Eastern (MID)

AF:

0.00391

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

64782

Other (OTH)

AF:

0.00156

AC:

AN:

1920

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000000129219), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.365

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000491

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000368

AC:

ExAC

AF:

0.000272

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.040

(source)

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

PhyloP100

-0.63

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

PromoterAI

-0.00060

Neutral

(source)

Varity_R

0.040

gMVP

0.041

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over