rs4480617

Variant names:

• chr12-81653429-G-C
• rs4480617
• NM_003625.5:c.303+23362C>G

Variant summary

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

The NM_003625.5(PPFIA2):​c.303+23362C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,886 control chromosomes in the GnomAD database, including 9,762 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 0.31 (9762 hom., cov: 31)
• Consequence: PPFIA2 NM_003625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIA2	NM_003625.5	c.303+23362C>G		intron_variant	Intron 4 of 32	ENST00000549396.6	NP_003616.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIA2	ENST00000549396.6	c.303+23362C>G		intron_variant	Intron 4 of 32	1	NM_003625.5	ENSP00000450337.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47503 AN: 151768 Hom.: 9751 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.313 AC: 47543 AN: 151886 Hom.: 9762 Cov.: 31 AF XY: 0.307 AC XY: 22810 AN XY: 74240

African (AFR) AF: 0.589 AC: 24378 AN: 41396

American (AMR) AF: 0.239 AC: 3641 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3468

East Asian (EAS) AF: 0.166 AC: 857 AN: 5154

South Asian (SAS) AF: 0.284 AC: 1365 AN: 4810

European-Finnish (FIN) AF: 0.189 AC: 1993 AN: 10564

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13834 AN: 67934

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.265 Hom.: 906

Bravo AF: 0.327

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		-0.38
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: rs4480617; hg19: chr12-82047208;