rs11742

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_014679.5(CEP57):c.753G>A(p.Pro251Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0434 in 1,611,970 control chromosomes in the GnomAD database, including 1,770 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. P251P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.032 ( 100 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1670 hom. )

Consequence

CEP57
NM_014679.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.896

Publications

5 publications found

Variant links:

Genes affected

CEP57 (HGNC:30794): (centrosomal protein 57) This gene encodes a cytoplasmic protein called Translokin. This protein localizes to the centrosome and has a function in microtubular stabilization. The N-terminal half of this protein is required for its centrosome localization and for its multimerization, and the C-terminal half is required for nucleating, bundling and anchoring microtubules to the centrosomes. This protein specifically interacts with fibroblast growth factor 2 (FGF2), sorting nexin 6, Ran-binding protein M and the kinesins KIF3A and KIF3B, and thus mediates the nuclear translocation and mitogenic activity of the FGF2. It also interacts with cyclin D1 and controls nucleocytoplasmic distribution of the cyclin D1 in quiescent cells. This protein is crucial for maintaining correct chromosomal number during cell division. Mutations in this gene cause mosaic variegated aneuploidy syndrome, a rare autosomal recessive disorder. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

CEP57 links:

MTMR2 (HGNC:7450): (myotubularin related protein 2) This gene is a member of the myotubularin family of phosphoinositide lipid phosphatases. The encoded protein possesses phosphatase activity towards phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

MTMR2 Gene-Disease associations (from GenCC):

demyelinating hereditary motor and sensory neuropathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Charcot-Marie-Tooth disease type 4B1
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

MTMR2 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 (REVEL=0.012).

BP6

Variant 11-95821924-G-A is Benign according to our data. Variant chr11-95821924-G-A is described in ClinVar as Benign. ClinVar VariationId is 414982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.896 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP57	NM_014679.5 link	c.753G>A	p.Pro251Pro	synonymous_variant	Exon 7 of 11	ENST00000325542.10	NP_055494.2	Q86XR8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP57	ENST00000325542.10 link	c.753G>A	p.Pro251Pro	synonymous_variant	Exon 7 of 11	1	NM_014679.5	ENSP00000317902.5		Q86XR8-1

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4942

AN:

151908

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00934

Gnomad AMI

AF:

0.0485

Gnomad AMR

AF:

0.0336

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00540

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0492

Gnomad OTH

AF:

0.0441

GnomAD2 exomes

AF:

0.0321

AC:

8045

AN:

250484

AF XY:

0.0325

show subpopulations

Gnomad AFR exome

AF:

0.00915

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0690

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.0482

Gnomad OTH exome

AF:

0.0356

GnomAD4 exome

AF:

0.0446

AC:

65063

AN:

1459944

Hom.:

1670

Cov.:

AF XY:

0.0439

AC XY:

31866

AN XY:

726352

show subpopulations

African (AFR)

AF:

0.00760

AC:

254

AN:

33442

American (AMR)

AF:

0.0235

AC:

1051

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0679

AC:

1771

AN:

26084

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39606

South Asian (SAS)

AF:

0.00781

AC:

673

AN:

86206

European-Finnish (FIN)

AF:

0.0258

AC:

1377

AN:

53336

Middle Eastern (MID)

AF:

0.0341

AC:

180

AN:

5284

European-Non Finnish (NFE)

AF:

0.0513

AC:

56986

AN:

1110982

Other (OTH)

AF:

0.0459

AC:

2770

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

2840

5681

8521

11362

14202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2084

4168

6252

8336

10420

<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:

0.0325

AC:

4939

AN:

152026

Hom.:

100

Cov.:

AF XY:

0.0312

AC XY:

2317

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.00931

AC:

386

AN:

41470

American (AMR)

AF:

0.0335

AC:

512

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0712

AC:

247

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00540

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0272

AC:

287

AN:

10558

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0492

AC:

3341

AN:

67968

Other (OTH)

AF:

0.0436

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

236

473

709

946

1182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0380

Hom.:

103

Bravo

AF:

0.0321

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Mosaic variegated aneuploidy syndrome 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.0

(source)

DANN

Benign

0.46

PhyloP100

-0.90

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over