chr13-102673963-G-A

Variant names:

• chr13-102673963-G-A
• rs661577
• NM_001330588.2:c.3372-320G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330588.2(TPP2):​c.3372-320G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,212 control chromosomes in the GnomAD database, including 50,803 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 0.81 (50803 hom., cov: 32)
• Consequence: TPP2 NM_001330588.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 5 publications found

Genes affected

TPP2 (HGNC:12016): (tripeptidyl peptidase 2) This gene encodes a mammalian peptidase that, at neutral pH, removes tripeptides from the N terminus of longer peptides. The protein has a specialized function that is essential for some MHC class I antigen presentation. The protein is a high molecular mass serine exopeptidase; the amino acid sequence surrounding the serine residue at the active site is similar to the peptidases of the subtilisin class rather than the trypsin class. [provided by RefSeq, Jul 2008]

TPP2 Gene-Disease associations (from GenCC):

• immunodeficiency 78 with autoimmunity and developmental delay

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330588.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPP2	NM_001330588.2	MANE Select	c.3372-320G>A		intron	N/A	NP_001317517.1
	TPP2	NM_001367947.1		c.3459-320G>A		intron	N/A	NP_001354876.1
	TPP2	NM_003291.4		c.3333-320G>A		intron	N/A	NP_003282.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPP2	ENST00000376052.5	TSL:5 MANE Select	c.3372-320G>A		intron	N/A	ENSP00000365220.3
	TPP2	ENST00000376065.8	TSL:1	c.3333-320G>A		intron	N/A	ENSP00000365233.4
	TPP2	ENST00000651823.1		n.128G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123689 AN: 152094 Hom.: 50762 Cov.: 32

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.879

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.833

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.813 AC: 123781 AN: 152212 Hom.: 50803 Cov.: 32 AF XY: 0.810 AC XY: 60250 AN XY: 74420

African (AFR) AF: 0.899 AC: 37351 AN: 41536

American (AMR) AF: 0.712 AC: 10873 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.879 AC: 3053 AN: 3472

East Asian (EAS) AF: 0.712 AC: 3682 AN: 5168

South Asian (SAS) AF: 0.777 AC: 3753 AN: 4832

European-Finnish (FIN) AF: 0.758 AC: 8029 AN: 10594

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54235 AN: 68014

Other (OTH) AF: 0.836 AC: 1766 AN: 2112

Alfa AF: 0.799 Hom.: 25533

Bravo AF: 0.813

Asia WGS AF: 0.767 AC: 2665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.25
PhyloP100		-0.64
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: rs661577; hg19: chr13-103326313;