chr8-12137674-G-A

Variant names:

• chr8-12137674-G-A
• rs201947742
• NM_201402.3:c.1087C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.779
• Publications: 0 publications found

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]

FAM66D (HGNC:24159): (family with sequence similarity 66 member D)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

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.1087C>T	p.Leu363Leu	synonymous	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-7749G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L2	ENST00000333796.4	TSL:6 MANE Select	c.1087C>T	p.Leu363Leu	synonymous	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-7965G>A		intron	N/A
	FAM66D	ENST00000653269.1		n.706-7749G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00134 AC: 189 AN: 140810 Hom.: 19 Cov.: 33

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

GnomAD2 exomes AF: 0.00156 AC: 366 AN: 234182 AF XY: 0.00165

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 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.: 75 AF XY: 0.00263 AC XY: 1821 AN XY: 691336

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

African (AFR) AF: 0.000226 AC: 7 AN: 30940

American (AMR) AF: 0.000547 AC: 23 AN: 42044

Ashkenazi Jewish (ASJ) AF: 0.00204 AC: 51 AN: 25048

East Asian (EAS) AF: 0.00 AC: 0 AN: 34122

South Asian (SAS) AF: 0.00272 AC: 210 AN: 77318

European-Finnish (FIN) AF: 0.0000391 AC: 2 AN: 51116

Middle Eastern (MID) AF: 0.000395 AC: 2 AN: 5066

European-Non Finnish (NFE) AF: 0.00303 AC: 3238 AN: 1068784

Other (OTH) AF: 0.00243 AC: 139 AN: 57126

⚠️ 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.

GnomAD4 genome AF: 0.00134 AC: 189 AN: 140902 Hom.: 19 Cov.: 33 AF XY: 0.00118 AC XY: 81 AN XY: 68470

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

African (AFR) AF: 0.000561 AC: 21 AN: 37450

American (AMR) AF: 0.000577 AC: 8 AN: 13876

Ashkenazi Jewish (ASJ) AF: 0.00179 AC: 6 AN: 3348

East Asian (EAS) AF: 0.00 AC: 0 AN: 4354

South Asian (SAS) AF: 0.00124 AC: 5 AN: 4030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 260

European-Non Finnish (NFE) AF: 0.00222 AC: 144 AN: 64932

Other (OTH) AF: 0.00 AC: 0 AN: 1938

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00102 Hom.: 2

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.0
DANN	Benign	0.53
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs201947742; hg19: chr8-11995183;