Genetic Variant NM_201402.3:c.291C>T (chr8-12138470-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_201402.3(USP17L2):c.291C>T(p.Cys97Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,540,268 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 21 hom. )

Consequence

USP17L2
NM_201402.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.362

Publications

0 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 8-12138470-G-A is Benign according to our data. Variant chr8-12138470-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2658428.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.362 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 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.291C>T	p.Cys97Cys	synonymous	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-6953G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP17L2	ENST00000333796.4	TSL:6 MANE Select	c.291C>T	p.Cys97Cys	synonymous	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
FAM66D	ENST00000434078.3	TSL:5	n.545-7169G>A		intron	N/A
FAM66D	ENST00000653269.1		n.706-6953G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000275

AC:

AN:

141668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000721

Gnomad ASJ

AF:

0.00598

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000616

Gnomad OTH

AF:

0.00104

GnomAD2 exomes

AF:

0.000357

AC:

AN:

229826

AF XY:

0.000310

show subpopulations

Gnomad AFR exome

AF:

0.000299

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00700

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000665

Gnomad OTH exome

AF:

0.000699

GnomAD4 exome

AF:

0.000204

AC:

285

AN:

1398600

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

144

AN XY:

694936

show subpopulations

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

African (AFR)

AF:

0.000435

AC:

AN:

32170

American (AMR)

AF:

0.00

AC:

AN:

42374

Ashkenazi Jewish (ASJ)

AF:

0.00719

AC:

181

AN:

25184

East Asian (EAS)

AF:

0.00

AC:

AN:

34974

South Asian (SAS)

AF:

0.00

AC:

AN:

78662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3862

European-Non Finnish (NFE)

AF:

0.0000419

AC:

AN:

1073516

Other (OTH)

AF:

0.000782

AC:

AN:

57550

⚠️ 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: 0.358

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:

0.000275

AC:

AN:

141668

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

AN XY:

68768

show subpopulations

African (AFR)

AF:

0.000314

AC:

AN:

38168

American (AMR)

AF:

0.0000721

AC:

AN:

13876

Ashkenazi Jewish (ASJ)

AF:

0.00598

AC:

AN:

3344

East Asian (EAS)

AF:

0.00

AC:

AN:

4384

South Asian (SAS)

AF:

0.00

AC:

AN:

4052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9814

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000616

AC:

AN:

64974

Other (OTH)

AF:

0.00104

AC:

AN:

1928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

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:

0.00117

Hom.:

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

BayesDel_noAF

Benign

-0.65

CADD

Benign

7.5

(source)

DANN

Benign

0.92

PhyloP100

0.36

PromoterAI

-0.0095

Neutral

(source)

Mutation Taster

=99/1

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