4-105369672-A-ACTTGGGGAAAAAGAGT

Variant summary

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

The NM_176869.3(PPA2):c.*52_*53insACTCTTTTTCCCCAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,492,210 control chromosomes in the GnomAD database, including 59,685 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8501 hom., cov: 0)
  • Exomes 𝑓: 0.27 (51184 hom.)
• Consequence: PPA2 NM_176869.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.560

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 4-105369672-A-ACTTGGGGAAAAAGAGT is Benign according to our data. Variant chr4-105369672-A-ACTTGGGGAAAAAGAGT is described in ClinVar as [Benign]. Clinvar id is 1269365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.*52_*53insACTCTTTTTCCCCAAG		3_prime_UTR_variant	12/12	ENST00000341695.10
PPA2	NM_006903.4	c.*52_*53insACTCTTTTTCCCCAAG		3_prime_UTR_variant	11/11
PPA2	NM_176866.2	c.*52_*53insACTCTTTTTCCCCAAG		3_prime_UTR_variant	8/8
PPA2	NM_176867.3	c.*52_*53insACTCTTTTTCCCCAAG		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.*52_*53insACTCTTTTTCCCCAAG		3_prime_UTR_variant	12/12	1	NM_176869.3	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49305 AN: 151770 Hom.: 8481 Cov.: 0

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.317

GnomAD4 exome AF: 0.270 AC: 362369 AN: 1340322 Hom.: 51184 Cov.: 27 AF XY: 0.269 AC XY: 180552 AN XY: 672354

Gnomad4 AFR exome AF: 0.439

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.325 AC: 49380 AN: 151888 Hom.: 8501 Cov.: 0 AF XY: 0.324 AC XY: 24026 AN XY: 74230

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.332

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.321

Alfa AF: 0.130 Hom.: 180

Asia WGS AF: 0.368 AC: 1283 AN: 3478

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16345; hg19: chr4-106290829;