Variant 19-7633434-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_174895.3(PCP2):c.24G>A(p.Thr8=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,575,464 control chromosomes in the GnomAD database, including 94,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7063 hom., cov: 33)

Exomes 𝑓: 0.35 ( 87663 hom. )

Consequence

PCP2
NM_174895.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0410

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:

STXBP2 (HGNC:):

STXBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 19-7633434-C-T is Benign according to our data. Variant chr19-7633434-C-T is described in ClinVar as [Benign]. Clinvar id is 403501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.041 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PCP2	NM_174895.3 linkuse as main transcript	c.24G>A	p.Thr8=	synonymous_variant	1/4	ENST00000311069.6	NP_777555.1
PCP2	XM_024451346.2 linkuse as main transcript	c.187G>A	p.Gly63Arg	missense_variant	1/5		XP_024307114.1
STXBP2	NM_001414484.1 linkuse as main transcript	c.-60+2588C>T		intron_variant			NP_001401413.1
PCP2	XM_006722639.4 linkuse as main transcript	c.-60-604G>A		intron_variant			XP_006722702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCP2	ENST00000311069.6 linkuse as main transcript	c.24G>A	p.Thr8=	synonymous_variant	1/4	1	NM_174895.3	ENSP00000310585	A1	Q8IVA1-1

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

44039

AN:

151720

Hom.:

7056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.367

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.297

AC:

55860

AN:

187902

Hom.:

8923

AF XY:

0.304

AC XY:

30620

AN XY:

100584

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.259

Gnomad EAS exome

AF:

0.182

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.413

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.330

GnomAD4 exome

AF:

0.346

AC:

492828

AN:

1423624

Hom.:

87663

Cov.:

AF XY:

0.345

AC XY:

243371

AN XY:

704550

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.190

Gnomad4 SAS exome

AF:

0.288

Gnomad4 FIN exome

AF:

0.408

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.327

GnomAD4 genome

AF:

0.290

AC:

44059

AN:

151840

Hom.:

7063

Cov.:

AF XY:

0.290

AC XY:

21564

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.245

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.195

Gnomad4 SAS

AF:

0.290

Gnomad4 FIN

AF:

0.417

Gnomad4 NFE

AF:

0.367

Gnomad4 OTH

AF:

0.302

Alfa

AF:

0.328

Hom.:

4432

Bravo

AF:

0.269

Asia WGS

AF:

0.250

AC:

873

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.2

DANN

Benign

0.61

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