rs2839223

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.2111G>A(p.Gly704Glu) variant causes a missense change. The variant allele was found at a frequency of 0.871 in 1,613,510 control chromosomes in the GnomAD database, including 613,305 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 58889 hom., cov: 33)

Exomes 𝑓: 0.87 ( 554416 hom. )

Consequence

PCNT
NM_006031.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.93

Publications

44 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=9.448388E-7).

BP6

Variant 21-46357148-G-A is Benign according to our data. Variant chr21-46357148-G-A is described in ClinVar as Benign. ClinVar VariationId is 159569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.2111G>A	p.Gly704Glu	missense_variant	Exon 13 of 47	ENST00000359568.10	NP_006022.3	O95613-1
PCNT	NM_001315529.2 link	c.1757G>A	p.Gly586Glu	missense_variant	Exon 13 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.2111G>A	p.Gly704Glu	missense_variant	Exon 13 of 47	1	NM_006031.6	ENSP00000352572.5		O95613-1

Frequencies

GnomAD3 genomes

AF:

0.879

AC:

133672

AN:

152134

Hom.:

58844

Cov.:

show subpopulations

Gnomad AFR

AF:

0.927

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.842

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.792

Gnomad FIN

AF:

0.842

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.876

Gnomad OTH

AF:

0.882

GnomAD2 exomes

AF:

0.855

AC:

214930

AN:

251322

AF XY:

0.852

show subpopulations

Gnomad AFR exome

AF:

0.927

Gnomad AMR exome

AF:

0.835

Gnomad ASJ exome

AF:

0.888

Gnomad EAS exome

AF:

0.816

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.875

Gnomad OTH exome

AF:

0.870

GnomAD4 exome

AF:

0.870

AC:

1271841

AN:

1461258

Hom.:

554416

Cov.:

AF XY:

0.867

AC XY:

630286

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.927

AC:

31017

AN:

33474

American (AMR)

AF:

0.834

AC:

37296

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.889

AC:

23241

AN:

26132

East Asian (EAS)

AF:

0.783

AC:

31078

AN:

39694

South Asian (SAS)

AF:

0.791

AC:

68243

AN:

86240

European-Finnish (FIN)

AF:

0.842

AC:

44955

AN:

53412

Middle Eastern (MID)

AF:

0.839

AC:

4833

AN:

5762

European-Non Finnish (NFE)

AF:

0.881

AC:

978634

AN:

1111448

Other (OTH)

AF:

0.870

AC:

52544

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

8815

17630

26444

35259

44074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21334

42668

64002

85336

106670

<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:

0.879

AC:

133775

AN:

152252

Hom.:

58889

Cov.:

AF XY:

0.873

AC XY:

64958

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.927

AC:

38520

AN:

41566

American (AMR)

AF:

0.842

AC:

12883

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.875

AC:

3039

AN:

3472

East Asian (EAS)

AF:

0.808

AC:

4175

AN:

5170

South Asian (SAS)

AF:

0.791

AC:

3820

AN:

4828

European-Finnish (FIN)

AF:

0.842

AC:

8929

AN:

10610

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.876

AC:

59562

AN:

67996

Other (OTH)

AF:

0.883

AC:

1864

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

842

1685

2527

3370

4212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.878

Hom.:

130998

Bravo

AF:

0.883

TwinsUK

AF:

0.878

AC:

3257

ALSPAC

AF:

0.883

AC:

3402

ESP6500AA

AF:

0.929

AC:

4094

ESP6500EA

AF:

0.876

AC:

7531

ExAC

AF:

0.856

AC:

103914

Asia WGS

AF:

0.806

AC:

2806

AN:

3478

EpiCase

AF:

0.874

EpiControl

AF:

0.875

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Microcephalic osteodysplastic primordial dwarfism type II

Benign:4

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

- -

Jan 13, 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

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

0.073

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.2

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.013

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.18

MetaRNN

Benign

9.4e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

PhyloP100

3.9

PrimateAI

Benign

0.42

PROVEAN

Benign

4.3

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.060

MPC

0.10

ClinPred

0.0018

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.014

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over