4-105369672-A-ACTTGGGGAAAAACAGT

Variant names:

• chr4-105369672-A-ACTTGGGGAAAAACAGT
• rs16345
• NM_176869.3:c.*52_*53insACTGTTTTTCCCCAAG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_176869.3(PPA2):​c.*52_*53insACTGTTTTTCCCCAAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PPA2 NM_176869.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 0 publications found

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]

PPA2 Gene-Disease associations (from GenCC):

• sudden cardiac failure, infantile

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• dilated cardiomyopathy

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176869.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPA2	NM_176869.3	MANE Select	c.*52_*53insACTGTTTTTCCCCAAG		3_prime_UTR	Exon 12 of 12	NP_789845.1	Q9H2U2-1
	PPA2	NM_006903.4		c.*52_*53insACTGTTTTTCCCCAAG		3_prime_UTR	Exon 11 of 11	NP_008834.3	Q9H2U2-3
	PPA2	NM_176866.2		c.*52_*53insACTGTTTTTCCCCAAG		3_prime_UTR	Exon 8 of 8	NP_789842.2	Q9H2U2-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPA2	ENST00000341695.10	TSL:1 MANE Select	c.*52_*53insACTGTTTTTCCCCAAG		3_prime_UTR	Exon 12 of 12	ENSP00000343885.5	Q9H2U2-1
	PPA2	ENST00000348706.9	TSL:1	c.*52_*53insACTGTTTTTCCCCAAG		3_prime_UTR	Exon 11 of 11	ENSP00000313061.8	Q9H2U2-3
	PPA2	ENST00000432483.6	TSL:1	c.*52_*53insACTGTTTTTCCCCAAG		3_prime_UTR	Exon 8 of 8	ENSP00000389957.2	Q9H2U2-6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs16345; hg19: chr4-106290829;