4-105370521-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_176869.3(PPA2):c.976+315del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 798,336 control chromosomes in the GnomAD database, including 546 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (399 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (147 hom.)
• Consequence: PPA2 NM_176869.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620

Genes affected

PPA2 (HGNC:28883): (inorganic pyrophosphatase 2) The protein encoded by this gene is localized to the mitochondrion, is highly similar to members of the inorganic pyrophosphatase (PPase) family, and contains the signature sequence essential for the catalytic activity of PPase. PPases catalyze the hydrolysis of pyrophosphate to inorganic phosphate, which is important for the phosphate metabolism of cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-105370521-GT-G is Benign according to our data. Variant chr4-105370521-GT-G is described in ClinVar as [Benign]. Clinvar id is 1177827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.976+315del		intron_variant		ENST00000341695.10
PPA2	NM_006903.4	c.889+315del		intron_variant
PPA2	NM_176866.2	c.670+315del		intron_variant
PPA2	NM_176867.3	c.478+315del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.976+315del		intron_variant		1	NM_176869.3	P1

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 5996 AN: 149966 Hom.: 399 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000838

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000519

Gnomad OTH AF: 0.0279

GnomAD4 exome AF: 0.00336 AC: 2180 AN: 648258 Hom.: 147 Cov.: 7 AF XY: 0.00317 AC XY: 957 AN XY: 302078

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.00706

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000320

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000301

Gnomad4 OTH exome AF: 0.00757

GnomAD4 genome AF: 0.0400 AC: 6001 AN: 150078 Hom.: 399 Cov.: 32 AF XY: 0.0385 AC XY: 2820 AN XY: 73288

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000840

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000519

Gnomad4 OTH AF: 0.0276

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.0463

Asia WGS AF: 0.00707 AC: 24 AN: 3410

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs147156921; hg19: chr4-106291678;