rs17685991

Variant names:

• chr12-81404878-G-A
• rs17685991
• NM_003625.5:c.762+909C>T

Variant summary

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

The ENST00000549396.6(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 ENST00000549396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000549396.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA2	NM_003625.5	MANE Select	c.762+909C>T		intron	N/A	NP_003616.2
	PPFIA2	NM_001220476.2		c.762+909C>T		intron	N/A	NP_001207405.1
	PPFIA2	NM_001220473.3		c.762+909C>T		intron	N/A	NP_001207402.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPFIA2	ENST00000549396.6	TSL:1 MANE Select	c.762+909C>T		intron	N/A	ENSP00000450337.1
	PPFIA2	ENST00000548586.5	TSL:1	c.762+909C>T		intron	N/A	ENSP00000449338.1
	PPFIA2	ENST00000550584.6	TSL:1	c.762+909C>T		intron	N/A	ENSP00000449558.2

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

African (AFR) AF: 0.0209 AC: 866 AN: 41488

American (AMR) AF: 0.0722 AC: 1102 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3464

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0357 AC: 172 AN: 4824

European-Finnish (FIN) AF: 0.176 AC: 1860 AN: 10550

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8207 AN: 67960

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.107 Hom.: 541

Bravo AF: 0.0770

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.44
PhyloP100		-0.067
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: rs17685991; hg19: chr12-81798657;