4-105370605-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_176869.3(PPA2):c.976+232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 970,802 control chromosomes in the GnomAD database, including 27,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4868 hom., cov: 32)
  • Exomes 𝑓: 0.23 (22797 hom.)
• Consequence: PPA2 NM_176869.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.308

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-105370605-C-T is Benign according to our data. Variant chr4-105370605-C-T is described in ClinVar as [Benign]. Clinvar id is 1296656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.976+232G>A		intron_variant		ENST00000341695.10
PPA2	NM_006903.4	c.889+232G>A		intron_variant
PPA2	NM_176866.2	c.670+232G>A		intron_variant
PPA2	NM_176867.3	c.478+232G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.976+232G>A		intron_variant		1	NM_176869.3	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 37862 AN: 150980 Hom.: 4855 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.232 AC: 190305 AN: 819704 Hom.: 22797 Cov.: 23 AF XY: 0.231 AC XY: 87457 AN XY: 378940

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.428

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.251 AC: 37930 AN: 151098 Hom.: 4868 Cov.: 32 AF XY: 0.251 AC XY: 18502 AN XY: 73734

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.264

Alfa AF: 0.130 Hom.: 226

Bravo AF: 0.256

Asia WGS AF: 0.355 AC: 1220 AN: 3432

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 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.2
Dann	Benign	0.48

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: rs36112402; hg19: chr4-106291762;