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GeneBe

rs1862514

chr19-7633434-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.041 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
PCP2NM_174895.3 linkuse as main transcriptc.24G>A p.Thr8= synonymous_variant 1/4 ENST00000311069.6
PCP2XM_024451346.2 linkuse as main transcriptc.187G>A p.Gly63Arg missense_variant 1/5
STXBP2NM_001414484.1 linkuse as main transcriptc.-60+2588C>T intron_variant
PCP2XM_006722639.4 linkuse as main transcriptc.-60-604G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PCP2ENST00000311069.6 linkuse as main transcriptc.24G>A p.Thr8= synonymous_variant 1/41 NM_174895.3 A1Q8IVA1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.290
AC:
44039
AN:
151720
Hom.:
7056
Cov.:
33
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.:
39
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.290
AC:
44059
AN:
151840
Hom.:
7063
Cov.:
33
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:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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 -

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.

Other links and lift over

dbSNP: rs1862514; hg19: chr19-7698320; COSMIC: COSV55403018; COSMIC: COSV55403018; API