NM_201402.3:c.786G>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate 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. 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 0.000036 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L2 NM_201402.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-12137975-C-A is Benign according to our data. Variant chr8-12137975-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 4280989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.

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>T	p.Pro262Pro	synonymous	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-7448C>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.786G>T	p.Pro262Pro	synonymous	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-7664C>A		intron	N/A
	FAM66D	ENST00000653269.1		n.706-7448C>A		intron	N/A

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

GnomAD2 exomes AF: 0.0000616 AC: 13 AN: 210994 AF XY: 0.0000347

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 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

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

African (AFR) AF: 0.00 AC: 0 AN: 29728

American (AMR) AF: 0.000167 AC: 7 AN: 41936

Ashkenazi Jewish (ASJ) AF: 0.0000803 AC: 2 AN: 24894

East Asian (EAS) AF: 0.000205 AC: 7 AN: 34074

South Asian (SAS) AF: 0.00 AC: 0 AN: 77036

European-Finnish (FIN) AF: 0.0000207 AC: 1 AN: 48314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3802

European-Non Finnish (NFE) AF: 0.0000115 AC: 12 AN: 1046356

Other (OTH) AF: 0.0000179 AC: 1 AN: 55978

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000321849), which strongly suggests a high chance of mosaicism in these individuals.

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

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

African (AFR) AF: 0.0000277 AC: 1 AN: 36038

American (AMR) AF: 0.0000736 AC: 1 AN: 13592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3300

East Asian (EAS) AF: 0.00 AC: 0 AN: 4196

South Asian (SAS) AF: 0.00 AC: 0 AN: 3920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.0000468 AC: 3 AN: 64168

Other (OTH) AF: 0.00 AC: 0 AN: 1880

⚠️ 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: 0.00 Hom.: 1175

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	-0.94
CADD	Benign	0.54
DANN	Benign	0.55
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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;