19-7632826-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_174895.3(PCP2):c.56G>T(p.Gly19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,549,988 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 73 hom. )

Consequence

PCP2
NM_174895.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.386

Variant links:

Genes affected

PCP2 (HGNC:30209): (Purkinje cell protein 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within rhodopsin mediated signaling pathway. Predicted to be located in neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

PCP2 links:

ENSG00000268400 (HGNC:):

ENSG00000268400 links:

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

STXBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020546913).

BP6

Variant 19-7632826-C-A is Benign according to our data. Variant chr19-7632826-C-A is described in ClinVar as [Benign]. Clinvar id is 770282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCP2	NM_174895.3 link	c.56G>T	p.Gly19Val	missense_variant	Exon 2 of 4	ENST00000311069.6	NP_777555.1	Q8IVA1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCP2	ENST00000311069.6 link	c.56G>T	p.Gly19Val	missense_variant	Exon 2 of 4	1	NM_174895.3	ENSP00000310585.4		Q8IVA1-1
ENSG00000268400	ENST00000698368.1 link	n.114+2167C>A		intron_variant	Intron 2 of 19			ENSP00000513686.1		A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

609

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.0106

AC:

1652

AN:

155332

Hom.:

AF XY:

0.00821

AC XY:

679

AN XY:

82672

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.0633

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.00878

GnomAD4 exome

AF:

0.00165

AC:

2309

AN:

1397740

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

993

AN XY:

690330

show subpopulations

Gnomad4 AFR exome

AF:

0.000660

Gnomad4 AMR exome

AF:

0.0588

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000139

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00403

AC:

613

AN:

152248

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.0356

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.000609

Hom.:

Bravo

AF:

0.00719

ESP6500AA

AF:

0.000919

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00355

AC:

396

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

.;T

Eigen

Benign

0.0059

Eigen_PC

Benign

0.031

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.085

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.030

D;D

Polyphen

0.94

.;P

Vest4

0.26

MPC

0.56

ClinPred

0.022

GERP RS

4.9

Varity_R

0.25

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over