4-105369463-T-C

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.*262A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 397,326 control chromosomes in the GnomAD database, including 2,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1201 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1582 hom.)
• Consequence: PPA2 NM_176869.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.401

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=-1.0).
• BP6: Variant 4-105369463-T-C is Benign according to our data. Variant chr4-105369463-T-C is described in ClinVar as [Benign]. Clinvar id is 1182538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPA2	NM_176869.3	c.*262A>G		3_prime_UTR_variant	12/12	ENST00000341695.10
PPA2	NM_006903.4	c.*262A>G		3_prime_UTR_variant	11/11
PPA2	NM_176866.2	c.*262A>G		3_prime_UTR_variant	8/8
PPA2	NM_176867.3	c.*262A>G		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPA2	ENST00000341695.10	c.*262A>G		3_prime_UTR_variant	12/12	1	NM_176869.3	P1
PPA2	ENST00000348706.9	c.*262A>G		3_prime_UTR_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18630 AN: 151994 Hom.: 1200 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0898

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.104 AC: 25410 AN: 245214 Hom.: 1582 Cov.: 0 AF XY: 0.101 AC XY: 13108 AN XY: 130314

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0903

Gnomad4 ASJ exome AF: 0.0811

Gnomad4 EAS exome AF: 0.00381

Gnomad4 SAS exome AF: 0.0607

Gnomad4 FIN exome AF: 0.0930

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.123 AC: 18642 AN: 152112 Hom.: 1201 Cov.: 32 AF XY: 0.119 AC XY: 8826 AN XY: 74370

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0898

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.0686

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.127

Alfa AF: 0.131 Hom.: 153

Bravo AF: 0.124

Asia WGS AF: 0.0510 AC: 180 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 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.16

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: rs112734002; hg19: chr4-106290620;