rs17245501

chr12-81342560-T-C

Variant summary

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

The NM_003625.5(PPFIA2):c.2263-1352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,178 control chromosomes in the GnomAD database, including 826 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 0.088 (826 hom., cov: 32)
• Consequence: PPFIA2 NM_003625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPFIA2	NM_003625.5	c.2263-1352A>G		intron_variant		ENST00000549396.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIA2	ENST00000549396.6	c.2263-1352A>G		intron_variant		1	NM_003625.5	A1

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13376 AN: 152060 Hom.: 826 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.0879 AC: 13375 AN: 152178 Hom.: 826 Cov.: 32 AF XY: 0.0903 AC XY: 6715 AN XY: 74394

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.0727

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0991

Alfa AF: 0.112 Hom.: 949

Bravo AF: 0.0785

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.1
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: rs17245501; hg19: chr12-81736339;