rs2073380

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006031.6(PCNT):c.9735A>C(p.Arg3245Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,004 control chromosomes in the GnomAD database, including 40,037 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3087 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36950 hom. )

Consequence

PCNT
NM_006031.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0960

Publications

40 publications found

Variant links:

Genes affected

PCNT (HGNC:16068): (pericentrin) The protein encoded by this gene binds to calmodulin and is expressed in the centrosome. It is an integral component of the pericentriolar material (PCM). The protein contains a series of coiled-coil domains and a highly conserved PCM targeting motif called the PACT domain near its C-terminus. The protein interacts with the microtubule nucleation component gamma-tubulin and is likely important to normal functioning of the centrosomes, cytoskeleton, and cell-cycle progression. Mutations in this gene cause Seckel syndrome-4 and microcephalic osteodysplastic primordial dwarfism type II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PCNT Gene-Disease associations (from GenCC):

microcephalic osteodysplastic primordial dwarfism type II
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
Moyamoya disease
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp

PCNT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011502206).

BP6

Variant 21-46443844-A-C is Benign according to our data. Variant chr21-46443844-A-C is described in ClinVar as Benign. ClinVar VariationId is 159697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.9735A>C	p.Arg3245Ser	missense_variant	Exon 45 of 47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.9144A>C	p.Arg3048Ser	missense_variant	Exon 45 of 47		NP_001302458.1	O95613-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 link	c.9735A>C	p.Arg3245Ser	missense_variant	Exon 45 of 47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28256

AN:

152032

Hom.:

3089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0800

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.205

GnomAD2 exomes

AF:

0.225

AC:

56476

AN:

251232

AF XY:

0.229

show subpopulations

Gnomad AFR exome

AF:

0.0756

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.434

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.219

AC:

319941

AN:

1460854

Hom.:

36950

Cov.:

AF XY:

0.221

AC XY:

160506

AN XY:

726764

show subpopulations

African (AFR)

AF:

0.0750

AC:

2508

AN:

33454

American (AMR)

AF:

0.163

AC:

7296

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

6059

AN:

26134

East Asian (EAS)

AF:

0.445

AC:

17672

AN:

39700

South Asian (SAS)

AF:

0.233

AC:

20090

AN:

86210

European-Finnish (FIN)

AF:

0.246

AC:

13161

AN:

53400

Middle Eastern (MID)

AF:

0.273

AC:

1436

AN:

5260

European-Non Finnish (NFE)

AF:

0.214

AC:

238069

AN:

1111656

Other (OTH)

AF:

0.226

AC:

13650

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

13409

26819

40228

53638

67047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8218

16436

24654

32872

41090

<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:

0.186

AC:

28257

AN:

152150

Hom.:

3087

Cov.:

AF XY:

0.186

AC XY:

13867

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0800

AC:

3321

AN:

41528

American (AMR)

AF:

0.166

AC:

2536

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

818

AN:

3468

East Asian (EAS)

AF:

0.428

AC:

2207

AN:

5158

South Asian (SAS)

AF:

0.242

AC:

1165

AN:

4820

European-Finnish (FIN)

AF:

0.241

AC:

2555

AN:

10594

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14844

AN:

67970

Other (OTH)

AF:

0.205

AC:

432

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1150

2299

3449

4598

5748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.213

Hom.:

5476

Bravo

AF:

0.178

TwinsUK

AF:

0.212

AC:

785

ALSPAC

AF:

0.218

AC:

842

ESP6500AA

AF:

0.0808

AC:

356

ESP6500EA

AF:

0.215

AC:

1849

ExAC

AF:

0.228

AC:

27660

Asia WGS

AF:

0.302

AC:

1049

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Microcephalic osteodysplastic primordial dwarfism type II

Benign:3

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 31, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

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

0.13

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.8

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.013

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

PhyloP100

-0.096

PrimateAI

Benign

0.48

PROVEAN

Benign

0.41

REVEL

Benign

0.013

Sift

Benign

0.73

Sift4G

Benign

0.70

Polyphen

0.010

Vest4

0.039

MutPred

0.32

Gain of phosphorylation at R3245 (P = 0.0025);

MPC

0.29

ClinPred

0.0098

GERP RS

-3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.25

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over