rs377180392

Variant names:

• chr12-81339194-C-A
• NM_003625.5:c.2534G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-81339194-C-A
• chr12-81339194-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003625.5(PPFIA2):​c.2534G>T​(p.Arg845Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,524 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PPFIA2 NM_003625.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIA2	NM_003625.5	c.2534G>T	p.Arg845Leu	missense_variant	Exon 21 of 33	ENST00000549396.6	NP_003616.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIA2	ENST00000549396.6	c.2534G>T	p.Arg845Leu	missense_variant	Exon 21 of 33	1	NM_003625.5	ENSP00000450337.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446524 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 719436

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;.;T;.;.;.;T;.;.;.;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;.;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.6	.;.;M;.;.;.;.;.;M;.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.3	D;.;D;D;D;D;.;D;D;D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.014	D;.;D;D;D;D;.;D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.96	.;.;D;.;.;.;.;.;.;.;.
Vest4		0.59
MutPred		0.38		.;.;Gain of helix (P = 0.0143);Gain of helix (P = 0.0143);.;.;.;.;Gain of helix (P = 0.0143);.;Gain of helix (P = 0.0143);
MVP		0.75
MPC		0.68
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.55
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-81732973;