rs61735818

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.7536G>A(p.Pro2512Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 1,612,398 control chromosomes in the GnomAD database, including 2,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 226 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2521 hom. )

Consequence

PCNT
NM_006031.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.59

Publications

10 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=-0.88).

BP6

Variant 21-46428436-G-A is Benign according to our data. Variant chr21-46428436-G-A is described in ClinVar as Benign. ClinVar VariationId is 138603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006031.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.7536G>A	p.Pro2512Pro	synonymous	Exon 35 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.7182G>A	p.Pro2394Pro	synonymous	Exon 35 of 47	NP_001302458.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PCNT	ENST00000359568.10	TSL:1 MANE Select	c.7536G>A	p.Pro2512Pro	synonymous	Exon 35 of 47	ENSP00000352572.5
PCNT	ENST00000480896.5	TSL:1	c.7182G>A	p.Pro2394Pro	synonymous	Exon 35 of 47	ENSP00000511989.1
PCNT	ENST00000695558.1		c.7569G>A	p.Pro2523Pro	synonymous	Exon 36 of 48	ENSP00000512015.1

Frequencies

GnomAD3 genomes

AF:

0.0475

AC:

7234

AN:

152240

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0252

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.0850

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0638

Gnomad OTH

AF:

0.0493

GnomAD2 exomes

AF:

0.0459

AC:

11394

AN:

248050

AF XY:

0.0455

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0718

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0867

Gnomad NFE exome

AF:

0.0620

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0552

AC:

80630

AN:

1460040

Hom.:

2521

Cov.:

AF XY:

0.0542

AC XY:

39372

AN XY:

726302

show subpopulations

African (AFR)

AF:

0.0227

AC:

759

AN:

33470

American (AMR)

AF:

0.0239

AC:

1068

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.0711

AC:

1854

AN:

26092

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.0139

AC:

1196

AN:

86152

European-Finnish (FIN)

AF:

0.0835

AC:

4352

AN:

52104

Middle Eastern (MID)

AF:

0.0322

AC:

185

AN:

5748

European-Non Finnish (NFE)

AF:

0.0613

AC:

68114

AN:

1111772

Other (OTH)

AF:

0.0513

AC:

3098

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

4507

9014

13520

18027

22534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2460

4920

7380

9840

12300

<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:

0.0475

AC:

7232

AN:

152358

Hom.:

226

Cov.:

AF XY:

0.0470

AC XY:

3502

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0252

AC:

1047

AN:

41590

American (AMR)

AF:

0.0334

AC:

512

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

247

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00911

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0850

AC:

903

AN:

10622

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0638

AC:

4340

AN:

68034

Other (OTH)

AF:

0.0488

AC:

103

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

360

721

1081

1442

1802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0495

Hom.:

119

Bravo

AF:

0.0429

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0558

EpiControl

AF:

0.0555

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Microcephalic osteodysplastic primordial dwarfism type II (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.058

(source)

DANN

Benign

0.41

PhyloP100

-3.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over