chr6-32158225-A-G

Position:

• chr6-32158225-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005155.7(PPT2):​c.710+301A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 341,516 control chromosomes in the GnomAD database, including 132,436 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.

• Frequency:
  • Genomes: 𝑓 0.89 (61043 hom., cov: 31)
  • Exomes 𝑓: 0.87 (71393 hom.)
• Consequence: PPT2 NM_005155.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363

Genes affected

PPT2 (HGNC:9326): (palmitoyl-protein thioesterase 2) This gene encodes a member of the palmitoyl-protein thioesterase family. The encoded glycosylated lysosomal protein has palmitoyl-CoA hydrolase activity in vitro, but does not hydrolyze palmitate from cysteine residues in proteins. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream EGFL8 (EGF-like-domain, multiple 8) gene. [provided by RefSeq, Feb 2011]

PPT2-EGFL8 (HGNC:48343): (PPT2-EGFL8 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring PPT2 (palmitoyl-protein thioesterase 2) and EGFL8 (EGF-like-domain, multiple 8) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

PPT2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPT2	NM_005155.7	c.710+301A>G		intron_variant		ENST00000324816.11	NP_005146.4
PPT2	NM_138717.3	c.728+301A>G		intron_variant			NP_619731.2
PPT2	NM_001204103.2	c.710+301A>G		intron_variant			NP_001191032.1
PPT2-EGFL8	NR_037861.1	n.1124+301A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPT2	ENST00000324816.11	c.710+301A>G		intron_variant		1	NM_005155.7	ENSP00000320528.6
PPT2-EGFL8	ENST00000422437.5	n.710+301A>G		intron_variant		5		ENSP00000457534.1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135996 AN: 152094 Hom.: 60988 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.935

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.867 AC: 164165 AN: 189306 Hom.: 71393 Cov.: 2 AF XY: 0.867 AC XY: 83879 AN XY: 96744

Gnomad4 AFR exome AF: 0.957

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 0.902

Gnomad4 EAS exome AF: 0.829

Gnomad4 SAS exome AF: 0.848

Gnomad4 FIN exome AF: 0.891

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.863

GnomAD4 genome AF: 0.894 AC: 136107 AN: 152210 Hom.: 61043 Cov.: 31 AF XY: 0.894 AC XY: 66545 AN XY: 74426

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.902

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.903

Alfa AF: 0.870 Hom.: 59176

Bravo AF: 0.901

Asia WGS AF: 0.816 AC: 2840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.2
DANN	Benign	0.81

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: rs3134603; hg19: chr6-32126002;