Genetic Variant PPFIA2:c.304-81336G>A (chr12-81539202-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003625.5(PPFIA2):c.304-81336G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,702 control chromosomes in the GnomAD database, including 32,111 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 0.65 ( 32111 hom., cov: 32)

Consequence

PPFIA2
NM_003625.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.52

Publications

6 publications found

Variant links:

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

PPFIA2 links:

PPFIA2-AS2 (HGNC:58195):

PPFIA2-AS2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003625.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPFIA2	NM_003625.5	MANE Select	c.304-81336G>A	intron	N/A	NP_003616.2
PPFIA2	NM_001220476.2		c.304-81336G>A	intron	N/A	NP_001207405.1
PPFIA2	NM_001220473.3		c.304-81336G>A	intron	N/A	NP_001207402.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PPFIA2	ENST00000549396.6	TSL:1 MANE Select	c.304-81336G>A	intron	N/A	ENSP00000450337.1
PPFIA2	ENST00000548586.5	TSL:1	c.304-81336G>A	intron	N/A	ENSP00000449338.1
PPFIA2	ENST00000550584.6	TSL:1	c.304-81336G>A	intron	N/A	ENSP00000449558.2

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98326

AN:

151586

Hom.:

32097

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.695

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.623

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

GnomAD4 genome

AF:

0.649

AC:

98389

AN:

151702

Hom.:

32111

Cov.:

AF XY:

0.654

AC XY:

48486

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.687

AC:

28400

AN:

41364

American (AMR)

AF:

0.641

AC:

9748

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1889

AN:

3462

East Asian (EAS)

AF:

0.755

AC:

3863

AN:

5116

South Asian (SAS)

AF:

0.732

AC:

3535

AN:

4830

European-Finnish (FIN)

AF:

0.695

AC:

7345

AN:

10564

Middle Eastern (MID)

AF:

0.650

AC:

191

AN:

294

European-Non Finnish (NFE)

AF:

0.611

AC:

41492

AN:

67858

Other (OTH)

AF:

0.627

AC:

1319

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1753

3505

5258

7010

8763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.614

Hom.:

36991

Bravo

AF:

0.644

Asia WGS

AF:

0.709

AC:

2464

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.078

(source)

DANN

Benign

0.53

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over