4-105370590-GA-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+246del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 961,456 control chromosomes in the GnomAD database, including 6,239 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1576 hom., cov: 30)
  • Exomes 𝑓: 0.10 (4663 hom.)
• Consequence: PPA2 NM_176869.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850

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 4-105370590-GA-G is Benign according to our data. Variant chr4-105370590-GA-G is described in ClinVar as [Benign]. Clinvar id is 1277752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.976+246del		intron_variant		ENST00000341695.10
PPA2	NM_006903.4	c.889+246del		intron_variant
PPA2	NM_176866.2	c.670+246del		intron_variant
PPA2	NM_176867.3	c.478+246del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.976+246del		intron_variant		1	NM_176869.3	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19211 AN: 146928 Hom.: 1564 Cov.: 30

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.0235

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.151

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.103 AC: 84035 AN: 814432 Hom.: 4663 Cov.: 0 AF XY: 0.103 AC XY: 38713 AN XY: 376570

Gnomad4 AFR exome AF: 0.0867

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.416

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.131 AC: 19267 AN: 147024 Hom.: 1576 Cov.: 30 AF XY: 0.135 AC XY: 9668 AN XY: 71372

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.137

Bravo AF: 0.132

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 11, 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: rs34420247; hg19: chr4-106291747;