rs17685991

Positions:

• chr12-81404878-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.762+909C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0864 in 152,048 control chromosomes in the GnomAD database, including 817 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 0.086 (817 hom., cov: 32)
• Consequence: PPFIA2 NM_003625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.762+909C>T		intron_variant		ENST00000549396.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPFIA2	ENST00000549396.6	c.762+909C>T		intron_variant		1	NM_003625.5	A1

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13150 AN: 151930 Hom.: 818 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.0864 AC: 13144 AN: 152048 Hom.: 817 Cov.: 32 AF XY: 0.0889 AC XY: 6604 AN XY: 74304

Gnomad4 AFR AF: 0.0209

Gnomad4 AMR AF: 0.0722

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0357

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0975

Alfa AF: 0.107 Hom.: 471

Bravo AF: 0.0770

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	-0.90
CADD	Benign	5.3
DANN	Benign	0.44

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: rs17685991; hg19: chr12-81798657;