dbSNP rs56241008: PPFIA2:p.Ala1119Ser (chr12-81268043-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003625.5(PPFIA2):c.3355G>T(p.Ala1119Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1119T) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPFIA2
NM_003625.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.66

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15074483).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
PPFIA2	NM_003625.5	MANE Select	c.3355G>T	p.Ala1119Ser	missense	Exon 29 of 33	NP_003616.2
PPFIA2	NM_001220476.2		c.3337G>T	p.Ala1113Ser	missense	Exon 28 of 32	NP_001207405.1	O75334-3
PPFIA2	NM_001220473.3		c.3355G>T	p.Ala1119Ser	missense	Exon 28 of 31	NP_001207402.1	G3V200

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPFIA2	ENST00000549396.6	TSL:1 MANE Select	c.3355G>T	p.Ala1119Ser	missense	Exon 29 of 33	ENSP00000450337.1	O75334-1
PPFIA2	ENST00000548586.5	TSL:1	c.3337G>T	p.Ala1113Ser	missense	Exon 28 of 31	ENSP00000449338.1	O75334-3
PPFIA2	ENST00000550584.6	TSL:1	c.3355G>T	p.Ala1119Ser	missense	Exon 28 of 31	ENSP00000449558.2	G3V200

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1445576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717328

African (AFR)

AF:

0.00

AC:

AN:

33142

American (AMR)

AF:

0.00

AC:

AN:

42656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25782

East Asian (EAS)

AF:

0.00

AC:

AN:

39278

South Asian (SAS)

AF:

0.00

AC:

AN:

83412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103218

Other (OTH)

AF:

0.00

AC:

AN:

59852

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.030

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.064

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Benign

0.034

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.65

MutationAssessor

Benign

-1.1

PhyloP100

3.7

PrimateAI

Uncertain

0.69

PROVEAN

Benign

1.2

REVEL

Uncertain

0.37

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.17

MutPred

0.66

Gain of MoRF binding (P = 0.0851)

MVP

0.39

MPC

1.1

ClinPred

0.60

GERP RS

5.9

Varity_R

0.25

gMVP

0.099

Mutation Taster

=71/29

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over