rs10506850

Variant names:

• chr12-81720984-C-T
• rs10506850
• NM_003625.5:c.249+32989G>A

Variant summary

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

The NM_003625.5(PPFIA2):​c.249+32989G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 150,420 control chromosomes in the GnomAD database, including 82 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 0.020 (82 hom., cov: 31)
• Consequence: PPFIA2 NM_003625.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIA2	NM_003625.5	c.249+32989G>A		intron_variant	Intron 3 of 32	ENST00000549396.6	NP_003616.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIA2	ENST00000549396.6	c.249+32989G>A		intron_variant	Intron 3 of 32	1	NM_003625.5	ENSP00000450337.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 2990 AN: 150306 Hom.: 81 Cov.: 31

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.00843

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00870

Gnomad OTH AF: 0.0184

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

GnomAD4 genome AF: 0.0199 AC: 2997 AN: 150420 Hom.: 82 Cov.: 31 AF XY: 0.0249 AC XY: 1826 AN XY: 73368

African (AFR) AF: 0.00489 AC: 201 AN: 41100

American (AMR) AF: 0.0346 AC: 520 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.00843 AC: 29 AN: 3442

East Asian (EAS) AF: 0.0770 AC: 393 AN: 5102

South Asian (SAS) AF: 0.0735 AC: 350 AN: 4760

European-Finnish (FIN) AF: 0.0808 AC: 836 AN: 10348

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00870 AC: 586 AN: 67356

Other (OTH) AF: 0.0226 AC: 47 AN: 2082

Alfa AF: 0.0140 Hom.: 9

Bravo AF: 0.0145

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		-0.22
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: rs10506850; hg19: chr12-82114763;