8-12138743-G-A

Variant names:

• chr8-12138743-G-A
• rs71237667
• NM_201402.3:c.18C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_201402.3(USP17L2):​c.18C>T​(p.Leu6Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 1,360,934 control chromosomes in the GnomAD database, including 11,565 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.062 (1268 hom., cov: 32)
  • Exomes 𝑓: 0.078 (10297 hom.)
• Consequence: USP17L2 NM_201402.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=0.036 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0903 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.18C>T	p.Leu6Leu	synonymous	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-6680G>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.18C>T	p.Leu6Leu	synonymous	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-6896G>A		intron	N/A
	FAM66D	ENST00000653269.1		n.706-6680G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 8675 AN: 138866 Hom.: 1267 Cov.: 32

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0480

Gnomad EAS AF: 0.000940

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.00719

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.0447

GnomAD2 exomes AF: 0.0621 AC: 11183 AN: 180120 AF XY: 0.0612

Gnomad AFR exome AF: 0.0162

Gnomad AMR exome AF: 0.0330

Gnomad ASJ exome AF: 0.0473

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.116

Gnomad NFE exome AF: 0.0919

Gnomad OTH exome AF: 0.0616

GnomAD4 exome AF: 0.0778 AC: 95051 AN: 1221980 Hom.: 10297 Cov.: 31 AF XY: 0.0760 AC XY: 46763 AN XY: 614988

African (AFR) AF: 0.0130 AC: 366 AN: 28192

American (AMR) AF: 0.0353 AC: 1479 AN: 41878

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 1172 AN: 24150

East Asian (EAS) AF: 0.000120 AC: 4 AN: 33346

South Asian (SAS) AF: 0.0146 AC: 1081 AN: 73926

European-Finnish (FIN) AF: 0.128 AC: 5844 AN: 45580

Middle Eastern (MID) AF: 0.0165 AC: 57 AN: 3460

European-Non Finnish (NFE) AF: 0.0888 AC: 81680 AN: 920112

Other (OTH) AF: 0.0656 AC: 3368 AN: 51336

GnomAD4 genome AF: 0.0624 AC: 8676 AN: 138954 Hom.: 1268 Cov.: 32 AF XY: 0.0622 AC XY: 4190 AN XY: 67312

African (AFR) AF: 0.0160 AC: 596 AN: 37160

American (AMR) AF: 0.0465 AC: 638 AN: 13708

Ashkenazi Jewish (ASJ) AF: 0.0480 AC: 159 AN: 3310

East Asian (EAS) AF: 0.000943 AC: 4 AN: 4242

South Asian (SAS) AF: 0.0139 AC: 55 AN: 3960

European-Finnish (FIN) AF: 0.125 AC: 1200 AN: 9608

Middle Eastern (MID) AF: 0.00775 AC: 2 AN: 258

European-Non Finnish (NFE) AF: 0.0922 AC: 5898 AN: 63958

Other (OTH) AF: 0.0437 AC: 84 AN: 1920

Alfa AF: 0.0434 Hom.: 151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.71
PhyloP100		0.036
PromoterAI		-0.026	Neutral
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: rs71237667; hg19: chr8-11996252; COSMIC: COSV61555853; COSMIC: COSV61555853;