4-105370667-G-A

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+170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 931,228 control chromosomes in the GnomAD database, including 28,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (6741 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21726 hom.)
• Consequence: PPA2 NM_176869.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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=-0.92).
• BP6: Variant 4-105370667-G-A is Benign according to our data. Variant chr4-105370667-G-A is described in ClinVar as [Benign]. Clinvar id is 1246086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.976+170C>T		intron_variant		ENST00000341695.10
PPA2	NM_006903.4	c.889+170C>T		intron_variant
PPA2	NM_176866.2	c.670+170C>T		intron_variant
PPA2	NM_176867.3	c.478+170C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.976+170C>T		intron_variant		1	NM_176869.3	P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43966 AN: 151542 Hom.: 6724 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.233 AC: 181490 AN: 779564 Hom.: 21726 Cov.: 13 AF XY: 0.231 AC XY: 83531 AN XY: 361168

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.290 AC: 44039 AN: 151664 Hom.: 6741 Cov.: 32 AF XY: 0.289 AC XY: 21377 AN XY: 74078

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.290

Alfa AF: 0.274 Hom.: 758

Bravo AF: 0.302

Asia WGS AF: 0.360 AC: 1235 AN: 3426

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.0
Dann	Benign	0.62

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: rs11301777; hg19: chr4-106291824;