19-7631742-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174895.3(PCP2):c.358G>A(p.Ala120Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,440,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PCP2
NM_174895.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700

Publications

4 publications found

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:

PET100 (HGNC:40038): (PET100 cytochrome c oxidase chaperone) Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by this gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

PET100 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 Gene-Disease associations (from GenCC):

familial hemophagocytic lymphohistiocytosis 5
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
hereditary hemophagocytic lymphohistiocytosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
microvillus inclusion disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

STXBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06522104).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174895.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCP2	NM_174895.3	MANE Select	c.358G>A	p.Ala120Thr	missense	Exon 4 of 4	NP_777555.1	Q8IVA1-1
PET100	NM_001171155.2	MANE Select	c.*186C>T		3_prime_UTR	Exon 4 of 4	NP_001164626.1	P0DJ07
PCP2	NM_001271830.2		c.310G>A	p.Ala104Thr	missense	Exon 4 of 4	NP_001258759.1	Q8IVA1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCP2	ENST00000311069.6	TSL:1 MANE Select	c.358G>A	p.Ala120Thr	missense	Exon 4 of 4	ENSP00000310585.4	Q8IVA1-1
PET100	ENST00000594797.6	TSL:1 MANE Select	c.*186C>T		3_prime_UTR	Exon 4 of 4	ENSP00000470539.1	P0DJ07
ENSG00000268400	ENST00000698368.1		n.114+1083C>T		intron	N/A	ENSP00000513686.1	A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000505

AC:

AN:

138688

AF XY:

0.0000405

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000837

Gnomad OTH exome

AF:

0.000363

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1288696

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

628166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27130

American (AMR)

AF:

0.00

AC:

AN:

23220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18034

East Asian (EAS)

AF:

0.00

AC:

AN:

33186

South Asian (SAS)

AF:

0.00

AC:

AN:

57634

European-Finnish (FIN)

AF:

0.0000217

AC:

AN:

46018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4980

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

1026020

Other (OTH)

AF:

0.0000381

AC:

AN:

52474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152000

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67990

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000336

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000434

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.12

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.68

M_CAP

Benign

0.0021

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

0.070

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.56

REVEL

Benign

0.045

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

0.081

Vest4

0.18

MVP

0.030

MPC

0.12

ClinPred

0.050

GERP RS

2.5

Varity_R

0.058

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over