rs2249057

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006031.6(PCNT):c.1542C>A(p.Ser514=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,613,610 control chromosomes in the GnomAD database, including 86,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7072 hom., cov: 33)

Exomes 𝑓: 0.33 ( 78942 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.00

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 21-46353189-C-A is Benign according to our data. Variant chr21-46353189-C-A is described in ClinVar as [Benign]. Clinvar id is 159566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46353189-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 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.1542C>A	p.Ser514=	synonymous_variant	10/47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2 linkuse as main transcript	c.1188C>A	p.Ser396=	synonymous_variant	10/47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 linkuse as main transcript	c.1542C>A	p.Ser514=	synonymous_variant	10/47	1	NM_006031.6	ENSP00000352572	P2	O95613-1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45312

AN:

151980

Hom.:

7070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.314

GnomAD3 exomes

AF:

0.314

AC:

78903

AN:

251360

Hom.:

12928

AF XY:

0.318

AC XY:

43259

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.331

Gnomad EAS exome

AF:

0.412

Gnomad SAS exome

AF:

0.304

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.339

Gnomad OTH exome

AF:

0.328

GnomAD4 exome

AF:

0.326

AC:

477176

AN:

1461512

Hom.:

78942

Cov.:

AF XY:

0.327

AC XY:

237774

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.317

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.323

GnomAD4 genome

AF:

0.298

AC:

45328

AN:

152098

Hom.:

7072

Cov.:

AF XY:

0.293

AC XY:

21822

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.255

Gnomad4 ASJ

AF:

0.326

Gnomad4 EAS

AF:

0.401

Gnomad4 SAS

AF:

0.311

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.333

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.315

Hom.:

9875

Bravo

AF:

0.294

EpiCase

AF:

0.326

EpiControl

AF:

0.339

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, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Jun 28, 2017	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

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	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0050

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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