rs2636697

Variant names:

• chr4-105376356-G-A
• rs2636697
• NM_176869.3:c.940-5483C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-105376356-G-A
• chr4-105376356-G-C
• chr4-105376356-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_176869.3(PPA2):​c.940-5483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 152,306 control chromosomes in the GnomAD database, including 70,024 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.96 (70024 hom., cov: 33)
• Consequence: PPA2 NM_176869.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPA2	NM_176869.3	c.940-5483C>T		intron_variant	Intron 10 of 11	ENST00000341695.10	NP_789845.1
PPA2	NM_006903.4	c.853-5483C>T		intron_variant	Intron 9 of 10		NP_008834.3
PPA2	NM_176866.2	c.634-5483C>T		intron_variant	Intron 6 of 7		NP_789842.2
PPA2	NM_176867.3	c.442-5483C>T		intron_variant	Intron 4 of 5		NP_789843.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPA2	ENST00000341695.10	c.940-5483C>T		intron_variant	Intron 10 of 11	1	NM_176869.3	ENSP00000343885.5

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145781 AN: 152188 Hom.: 69970 Cov.: 33

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.957

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.958 AC: 145894 AN: 152306 Hom.: 70024 Cov.: 33 AF XY: 0.953 AC XY: 70967 AN XY: 74474

African (AFR) AF: 0.992 AC: 41252 AN: 41582

American (AMR) AF: 0.924 AC: 14130 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3369 AN: 3472

East Asian (EAS) AF: 0.778 AC: 4026 AN: 5178

South Asian (SAS) AF: 0.862 AC: 4163 AN: 4828

European-Finnish (FIN) AF: 0.941 AC: 9995 AN: 10626

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65771 AN: 68020

Other (OTH) AF: 0.957 AC: 2022 AN: 2112

Alfa AF: 0.958 Hom.: 11270

Bravo AF: 0.957

Asia WGS AF: 0.842 AC: 2928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2636697; hg19: chr4-106297513;