rs2249057

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006031.6(PCNT):c.1542C>A(p.Ser514Ser) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. S514S) has been classified as Likely 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

Publications

37 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 -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 VariationId is 159566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PCNT	NM_006031.6 link	c.1542C>A	p.Ser514Ser	synonymous_variant	Exon 10 of 47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2 link	c.1188C>A	p.Ser396Ser	synonymous_variant	Exon 10 of 47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10 link	c.1542C>A	p.Ser514Ser	synonymous_variant	Exon 10 of 47	1	NM_006031.6	ENSP00000352572.5

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

GnomAD2 exomes

AF:

0.314

AC:

78903

AN:

251360

AF XY:

0.318

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 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

African (AFR)

AF:

0.233

AC:

7785

AN:

33476

American (AMR)

AF:

0.221

AC:

9905

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

8594

AN:

26134

East Asian (EAS)

AF:

0.417

AC:

16547

AN:

39698

South Asian (SAS)

AF:

0.309

AC:

26678

AN:

86248

European-Finnish (FIN)

AF:

0.317

AC:

16925

AN:

53340

Middle Eastern (MID)

AF:

0.379

AC:

2185

AN:

5768

European-Non Finnish (NFE)

AF:

0.332

AC:

369054

AN:

1111742

Other (OTH)

AF:

0.323

AC:

19503

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

19311

38622

57932

77243

96554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11906

23812

35718

47624

59530

<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:

0.298

AC:

45328

AN:

152098

Hom.:

7072

Cov.:

AF XY:

0.293

AC XY:

21822

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.234

AC:

9697

AN:

41480

American (AMR)

AF:

0.255

AC:

3897

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1132

AN:

3472

East Asian (EAS)

AF:

0.401

AC:

2078

AN:

5178

South Asian (SAS)

AF:

0.311

AC:

1498

AN:

4820

European-Finnish (FIN)

AF:

0.309

AC:

3265

AN:

10568

Middle Eastern (MID)

AF:

0.391

AC:

115

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22635

AN:

67996

Other (OTH)

AF:

0.314

AC:

662

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1662

3324

4985

6647

8309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.312

Hom.:

12075

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

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Jun 28, 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.

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0050

(source)

DANN

Benign

0.46

PhyloP100

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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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