rs2839217

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.721-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,591,548 control chromosomes in the GnomAD database, including 107,725 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8407 hom., cov: 34)

Exomes 𝑓: 0.37 ( 99318 hom. )

Consequence

PCNT
NM_006031.6 splice_region, intron

Scores

Splicing: ADA: 0.000007724

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.90

Publications

19 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: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P, 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 (BayesDel_noAF=-0.98).

BP6

Variant 21-46346736-G-A is Benign according to our data. Variant chr21-46346736-G-A is described in ClinVar as Benign. ClinVar VariationId is 159653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	NM_006031.6	MANE Select	c.721-7G>A		splice_region intron	N/A	NP_006022.3
	PCNT	NM_001315529.2		c.367-7G>A		splice_region intron	N/A	NP_001302458.1	O95613-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PCNT	ENST00000359568.10	TSL:1 MANE Select	c.721-7G>A	splice_region intron	N/A	ENSP00000352572.5	O95613-1
PCNT	ENST00000480896.5	TSL:1	c.367-7G>A	splice_region intron	N/A	ENSP00000511989.1	O95613-2
PCNT	ENST00000695558.1		c.721-7G>A	splice_region intron	N/A	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48768

AN:

152046

Hom.:

8407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.340

AC:

71850

AN:

211102

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.427

Gnomad EAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.382

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.369

AC:

530683

AN:

1439384

Hom.:

99318

Cov.:

AF XY:

0.368

AC XY:

262840

AN XY:

713858

show subpopulations

African (AFR)

AF:

0.207

AC:

6881

AN:

33284

American (AMR)

AF:

0.239

AC:

9790

AN:

41046

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

10775

AN:

25564

East Asian (EAS)

AF:

0.416

AC:

16223

AN:

38972

South Asian (SAS)

AF:

0.318

AC:

26280

AN:

82708

European-Finnish (FIN)

AF:

0.339

AC:

17277

AN:

50912

Middle Eastern (MID)

AF:

0.407

AC:

2101

AN:

5162

European-Non Finnish (NFE)

AF:

0.381

AC:

419858

AN:

1102162

Other (OTH)

AF:

0.361

AC:

21498

AN:

59574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

18271

36541

54812

73082

91353

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13156

26312

39468

52624

65780

<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:

0.321

AC:

48777

AN:

152164

Hom.:

8407

Cov.:

AF XY:

0.315

AC XY:

23451

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.211

AC:

8747

AN:

41528

American (AMR)

AF:

0.280

AC:

4280

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1450

AN:

3472

East Asian (EAS)

AF:

0.401

AC:

2072

AN:

5166

South Asian (SAS)

AF:

0.315

AC:

1519

AN:

4818

European-Finnish (FIN)

AF:

0.331

AC:

3502

AN:

10590

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.382

AC:

25944

AN:

67992

Other (OTH)

AF:

0.356

AC:

752

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1636

3271

4907

6542

8178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.357

Hom.:

26988

Bravo

AF:

0.315

Asia WGS

AF:

0.344

AC:

1198

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microcephalic osteodysplastic primordial dwarfism type II (4)

not provided (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.4

(source)

DANN

Benign

0.30

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000077

dbscSNV1_RF

Benign

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over