rs10778826

Positions:

• chr12-81709075-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003625.5(PPFIA2):​c.250-32231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,946 control chromosomes in the GnomAD database, including 8,709 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 0.32 (8709 hom., cov: 32)
• Consequence: PPFIA2 NM_003625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

Genes affected

PPFIA2 (HGNC:9246): (PTPRF interacting protein alpha 2) The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein has been shown to bind the calcium/calmodulin-dependent serine protein kinase (MAGUK family) protein (also known as CASK) and proposed to regulate higher-order brain functions in mammals. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPFIA2	NM_003625.5	c.250-32231C>T		intron_variant		ENST00000549396.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIA2	ENST00000549396.6	c.250-32231C>T		intron_variant		1	NM_003625.5	A1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48556 AN: 151828 Hom.: 8711 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.320 AC: 48568 AN: 151946 Hom.: 8709 Cov.: 32 AF XY: 0.312 AC XY: 23174 AN XY: 74276

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.365

Alfa AF: 0.401 Hom.: 24765

Bravo AF: 0.323

Asia WGS AF: 0.232 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.064
DANN	Benign	0.49

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: rs10778826; hg19: chr12-82102854;