4-105369454-A-AC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_176869.3(PPA2):c.*270_*271insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 377,426 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: PPA2 NM_176869.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.460

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 4-105369454-A-AC is Benign according to our data. Variant chr4-105369454-A-AC is described in ClinVar as [Likely_benign]. Clinvar id is 1213559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00773 (1175/152006) while in subpopulation AFR AF= 0.0259 (1073/41360). AF 95% confidence interval is 0.0247. There are 20 homozygotes in gnomad4. There are 574 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.*270_*271insG		3_prime_UTR_variant	12/12	ENST00000341695.10
PPA2	NM_006903.4	c.*270_*271insG		3_prime_UTR_variant	11/11
PPA2	NM_176866.2	c.*270_*271insG		3_prime_UTR_variant	8/8
PPA2	NM_176867.3	c.*270_*271insG		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.*270_*271insG		3_prime_UTR_variant	12/12	1	NM_176869.3	P1
PPA2	ENST00000348706.9	c.*270_*271insG		3_prime_UTR_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.00764 AC: 1160 AN: 151888 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00413

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00107 AC: 241 AN: 225420 Hom.: 1 Cov.: 0 AF XY: 0.00107 AC XY: 128 AN XY: 119876

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.00220

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000841

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000173

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.00773 AC: 1175 AN: 152006 Hom.: 20 Cov.: 32 AF XY: 0.00772 AC XY: 574 AN XY: 74322

Gnomad4 AFR AF: 0.0259

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00598 Hom.: 1

Bravo AF: 0.00855

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 31, 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: rs201046593; hg19: chr4-106290611;