NM_003625.5:c.645+6659A>G

Variant names:

• chr12-81433313-T-C
• rs17306116
• NM_003625.5:c.645+6659A>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.645+6659A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,254 control chromosomes in the GnomAD database, including 842 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 0.089 (842 hom., cov: 32)
• Consequence: PPFIA2 NM_003625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 1 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

ENSG00000258162 (HGNC:58195):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIA2	NM_003625.5	c.645+6659A>G		intron_variant	Intron 7 of 32	ENST00000549396.6	NP_003616.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIA2	ENST00000549396.6	c.645+6659A>G		intron_variant	Intron 7 of 32	1	NM_003625.5	ENSP00000450337.1

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13492 AN: 152136 Hom.: 842 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0886 AC: 13490 AN: 152254 Hom.: 842 Cov.: 32 AF XY: 0.0910 AC XY: 6771 AN XY: 74446

African (AFR) AF: 0.0242 AC: 1006 AN: 41566

American (AMR) AF: 0.0749 AC: 1145 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 493 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0364 AC: 176 AN: 4832

European-Finnish (FIN) AF: 0.176 AC: 1865 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8349 AN: 68004

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.103 Hom.: 145

Bravo AF: 0.0795

Asia WGS AF: 0.0180 AC: 61 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.22
PhyloP100		-0.27
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: rs17306116; hg19: chr12-81827092;