8-12137975-C-A

Variant names:

• chr8-12137975-C-A
• rs74614551
• NM_201402.3:c.786G>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_201402.3(USP17L2):​c.786G>T​(p.Pro262Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L2 NM_201402.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP17L2	NM_201402.3	c.786G>T	p.Pro262Pro	synonymous_variant	Exon 1 of 1	ENST00000333796.4	NP_958804.2
FAM66D	NR_027425.1	n.609-7448C>A		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USP17L2	ENST00000333796.4	c.786G>T	p.Pro262Pro	synonymous_variant	Exon 1 of 1	6	NM_201402.3	ENSP00000333329.3

Frequencies

GnomAD3 genomes AF: 0.0000363 AC: 5 AN: 137822 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000736

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000468

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000616 AC: 13 AN: 210994 Hom.: 3 AF XY: 0.0000347 AC XY: 4 AN XY: 115356

Gnomad AFR exome AF: 0.0000869

Gnomad AMR exome AF: 0.000227

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000210

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000206

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000220 AC: 30 AN: 1362118 Hom.: 5 Cov.: 51 AF XY: 0.0000147 AC XY: 10 AN XY: 678204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000167

Gnomad4 ASJ exome AF: 0.0000803

Gnomad4 EAS exome AF: 0.000205

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.0000115

Gnomad4 OTH exome AF: 0.0000179

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000363 AC: 5 AN: 137822 Hom.: 0 Cov.: 32 AF XY: 0.0000600 AC XY: 4 AN XY: 66696

Gnomad4 AFR AF: 0.0000277

Gnomad4 AMR AF: 0.0000736

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000468

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.54
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs74614551; hg19: chr8-11995484;