rs10778826

Variant names:

• chr12-81709075-G-A
• rs10778826
• NM_003625.5:c.250-32231C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

PPFIA2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003625.5. 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
	PPFIA2	NM_003625.5	MANE Select	c.250-32231C>T		intron	N/A	NP_003616.2
	PPFIA2	NM_001220476.2		c.250-32231C>T		intron	N/A	NP_001207405.1	O75334-3
	PPFIA2	NM_001220473.3		c.250-32231C>T		intron	N/A	NP_001207402.1	G3V200

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA2	ENST00000549396.6	TSL:1 MANE Select	c.250-32231C>T		intron	N/A	ENSP00000450337.1	O75334-1
	PPFIA2	ENST00000548586.5	TSL:1	c.250-32231C>T		intron	N/A	ENSP00000449338.1	O75334-3
	PPFIA2	ENST00000550584.6	TSL:1	c.250-32231C>T		intron	N/A	ENSP00000449558.2	G3V200

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

African (AFR) AF: 0.164 AC: 6792 AN: 41454

American (AMR) AF: 0.370 AC: 5649 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1100 AN: 5142

South Asian (SAS) AF: 0.307 AC: 1479 AN: 4814

European-Finnish (FIN) AF: 0.262 AC: 2768 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28126 AN: 67938

Other (OTH) AF: 0.365 AC: 769 AN: 2106

Alfa AF: 0.386 Hom.: 36433

Bravo AF: 0.323

Asia WGS AF: 0.232 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.064
DANN	Benign	0.49
PhyloP100		-1.6
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: rs10778826; hg19: chr12-82102854;