rs2839223

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 159569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46357148-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
PCNT	NM_006031.6 linkuse as main transcript	c.2111G>A	p.Gly704Glu	missense_variant	13/47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2 linkuse as main transcript	c.1757G>A	p.Gly586Glu	missense_variant	13/47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.2111G>A	p.Gly704Glu	missense_variant	13/47	1	NM_006031.6	ENSP00000352572	P2	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

GnomAD3 exomes

AF:

0.855

AC:

214930

AN:

251322

Hom.:

92191

AF XY:

0.852

AC XY:

115742

AN XY:

135868

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 SAS exome

AF:

0.786

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

Gnomad4 AFR exome

AF:

0.927

Gnomad4 AMR exome

AF:

0.834

Gnomad4 ASJ exome

AF:

0.889

Gnomad4 EAS exome

AF:

0.783

Gnomad4 SAS exome

AF:

0.791

Gnomad4 FIN exome

AF:

0.842

Gnomad4 NFE exome

AF:

0.881

Gnomad4 OTH exome

AF:

0.870

GnomAD4 genome

AF:

0.879

AC:

133775

AN:

152252

Hom.:

58889

Cov.:

AF XY:

0.873

AC XY:

64958

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.927

Gnomad4 AMR

AF:

0.842

Gnomad4 ASJ

AF:

0.875

Gnomad4 EAS

AF:

0.808

Gnomad4 SAS

AF:

0.791

Gnomad4 FIN

AF:

0.842

Gnomad4 NFE

AF:

0.876

Gnomad4 OTH

AF:

0.883

Alfa

AF:

0.876

Hom.:

92013

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

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	May 31, 2017	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

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

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

MutationTaster

Benign

1.0

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

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

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