13-24906007-G-A

Variant names:

Variant summary

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

The NM_018451.5(CPAP):c.2031C>T(p.Ala677Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 1,614,032 control chromosomes in the GnomAD database, including 336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 65 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 271 hom. )

Consequence

CPAP
NM_018451.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.741

Publications

6 publications found

Variant links:

Genes affected

CPAP (HGNC:17272): (centromere protein J) This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

CPAP Gene-Disease associations (from GenCC):

microcephaly 6 with or without short stature
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
microcephaly 6, primary, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal recessive primary microcephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CPAP 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=-0.76).

BP6

Variant 13-24906007-G-A is Benign according to our data. Variant chr13-24906007-G-A is described in ClinVar as Benign. ClinVar VariationId is 158199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.741 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAP	NM_018451.5 link	c.2031C>T	p.Ala677Ala	synonymous_variant	Exon 7 of 17	ENST00000381884.9	NP_060921.3	Q9HC77-1A8K8P1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CENPJ	ENST00000381884.9 link	c.2031C>T	p.Ala677Ala	synonymous_variant	Exon 7 of 17	1	NM_018451.5	ENSP00000371308.4	Q9HC77-1
CENPJ	ENST00000616936.4 link	n.2031C>T		non_coding_transcript_exon_variant	Exon 7 of 16	1		ENSP00000477511.1	Q9HC77-2
CENPJ	ENST00000545981.6 link	n.2031C>T		non_coding_transcript_exon_variant	Exon 7 of 18	2		ENSP00000441090.2	F6VUX8

Frequencies

GnomAD3 genomes

AF:

0.0165

AC:

2502

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0791

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.0197

GnomAD2 exomes

AF:

0.0147

AC:

3696

AN:

251250

AF XY:

0.0124

show subpopulations

Gnomad AFR exome

AF:

0.0404

Gnomad AMR exome

AF:

0.0313

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0850

Gnomad FIN exome

AF:

0.00458

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.00930

GnomAD4 exome

AF:

0.00590

AC:

8621

AN:

1461842

Hom.:

271

Cov.:

AF XY:

0.00549

AC XY:

3995

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0386

AC:

1292

AN:

33480

American (AMR)

AF:

0.0296

AC:

1323

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26134

East Asian (EAS)

AF:

0.102

AC:

4061

AN:

39700

South Asian (SAS)

AF:

0.00307

AC:

265

AN:

86258

European-Finnish (FIN)

AF:

0.00530

AC:

283

AN:

53410

Middle Eastern (MID)

AF:

0.00902

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000725

AC:

806

AN:

1112004

Other (OTH)

AF:

0.00861

AC:

520

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

522

1044

1566

2088

2610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.0165

AC:

2505

AN:

152190

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1270

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0382

AC:

1586

AN:

41504

American (AMR)

AF:

0.0215

AC:

329

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.0791

AC:

409

AN:

5170

South Asian (SAS)

AF:

0.00539

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68024

Other (OTH)

AF:

0.0190

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

122

244

366

488

610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00714

Hom.:

Bravo

AF:

0.0200

Asia WGS

AF:

0.0390

AC:

135

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 27, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Seckel syndrome 4

Benign:1

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. -

Microcephaly 6, primary, autosomal recessive

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

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

-0.76

CADD

Benign

3.9

(source)

DANN

Benign

0.46

PhyloP100

-0.74

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