chr8-12137975-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_201402.3(USP17L2):​c.786G>C​(p.Pro262Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P262P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USP17L2 NM_201402.3 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• 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>C	p.Pro262Pro	synonymous	Exon 1 of 1	NP_958804.2	Q6R6M4
	FAM66D	NR_027425.1		n.609-7448C>G		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>C	p.Pro262Pro	synonymous	Exon 1 of 1	ENSP00000333329.3	Q6R6M4
	FAM66D	ENST00000434078.3	TSL:5	n.545-7664C>G		intron	N/A
	FAM66D	ENST00000653269.1		n.706-7448C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1362194 Hom.: 0 Cov.: 51 AF XY: 0.00 AC XY: 0 AN XY: 678238

African (AFR) AF: 0.00 AC: 0 AN: 29730

American (AMR) AF: 0.00 AC: 0 AN: 41936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24896

East Asian (EAS) AF: 0.00 AC: 0 AN: 34074

South Asian (SAS) AF: 0.00 AC: 0 AN: 77040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48326

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046412

Other (OTH) AF: 0.00 AC: 0 AN: 55978

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.46
PhyloP100		-1.4

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;