11-7620968-A-G

Position:

• chr11-7620968-A-G

Variant summary

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

The ENST00000299492.9(PPFIBP2):​c.652A>G​(p.Lys218Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPFIBP2 ENST00000299492.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65

Genes affected

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

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/exons	MANE	Protein	UniProt
PPFIBP2	NM_003621.5	c.652A>G	p.Lys218Glu	missense_variant	7/24	ENST00000299492.9	NP_003612.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPFIBP2	ENST00000299492.9	c.652A>G	p.Lys218Glu	missense_variant	7/24	1	NM_003621.5	ENSP00000299492	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.652A>G (p.K218E) alteration is located in exon 7 (coding exon 6) of the PPFIBP2 gene. This alteration results from a A to G substitution at nucleotide position 652, causing the lysine (K) at amino acid position 218 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;.;.;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.7	D;D;D;.;D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D;D;.;D;D;D
Sift4G	Uncertain	0.023	D;D;D;.;D;D;D
Polyphen		0.97	D;.;.;.;.;.;.
Vest4		0.52
MutPred		0.45		Loss of ubiquitination at K218 (P = 0.0043);.;.;.;.;.;.;
MVP		0.78
MPC		0.060
ClinPred		0.91	D
GERP RS		5.2
Varity_R		0.79
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-7642199;