8-12137975-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_201402.3(USP17L2):​c.786G>A​(p.Pro262Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,475,284 control chromosomes in the GnomAD database, including 131,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P262P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.42 (11091 hom., cov: 32)
  • Exomes 𝑓: 0.45 (120118 hom.)
• Consequence: USP17L2 NM_201402.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 8-12137975-C-T is Benign according to our data. Variant chr8-12137975-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 768228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

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.786G>A	p.Pro262Pro	synonymous	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-7448C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP17L2	ENST00000333796.4	TSL:6 MANE Select	c.786G>A	p.Pro262Pro	synonymous	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-7664C>T		intron	N/A
	FAM66D	ENST00000653269.1		n.706-7448C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.417 AC: 56611 AN: 135626 Hom.: 11088 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.449

GnomAD2 exomes AF: 0.457 AC: 96461 AN: 210994 AF XY: 0.452

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.559

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.377

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.466

GnomAD4 exome AF: 0.446 AC: 597654 AN: 1339572 Hom.: 120118 Cov.: 51 AF XY: 0.445 AC XY: 297283 AN XY: 667304

African (AFR) AF: 0.297 AC: 8715 AN: 29328

American (AMR) AF: 0.558 AC: 23297 AN: 41768

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 12232 AN: 24698

East Asian (EAS) AF: 0.377 AC: 12796 AN: 33914

South Asian (SAS) AF: 0.414 AC: 31665 AN: 76544

European-Finnish (FIN) AF: 0.511 AC: 24435 AN: 47838

Middle Eastern (MID) AF: 0.448 AC: 1691 AN: 3776

European-Non Finnish (NFE) AF: 0.446 AC: 458302 AN: 1026526

Other (OTH) AF: 0.444 AC: 24521 AN: 55180

GnomAD4 genome AF: 0.417 AC: 56634 AN: 135712 Hom.: 11091 Cov.: 32 AF XY: 0.421 AC XY: 27624 AN XY: 65690

African (AFR) AF: 0.300 AC: 10625 AN: 35410

American (AMR) AF: 0.501 AC: 6729 AN: 13434

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1636 AN: 3248

East Asian (EAS) AF: 0.367 AC: 1524 AN: 4148

South Asian (SAS) AF: 0.399 AC: 1539 AN: 3858

European-Finnish (FIN) AF: 0.524 AC: 4993 AN: 9528

Middle Eastern (MID) AF: 0.414 AC: 106 AN: 256

European-Non Finnish (NFE) AF: 0.448 AC: 28301 AN: 63152

Other (OTH) AF: 0.450 AC: 839 AN: 1864

Alfa AF: 0.352 Hom.: 1175

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.9
DANN	Benign	0.66
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs74614551; hg19: chr8-11995484; COSMIC: COSV61555943; COSMIC: COSV61555943;