rs2293277

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_018131.5(CEP55):c.1133A>T(p.His378Leu) variant causes a missense change. The variant allele was found at a frequency of 0.73 in 1,613,748 control chromosomes in the GnomAD database, including 439,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 33484 hom., cov: 33)

Exomes 𝑓: 0.74 ( 405582 hom. )

Consequence

CEP55
NM_018131.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.13

Publications

43 publications found

Variant links:

Genes affected

CEP55 (HGNC:1161): (centrosomal protein 55) Enables identical protein binding activity. Involved in cranial skeletal system development; establishment of protein localization; and midbody abscission. Acts upstream of or within mitotic cytokinesis. Located in Flemming body; centriolar satellite; and plasma membrane. Implicated in multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly. [provided by Alliance of Genome Resources, Apr 2022]

CEP55 Gene-Disease associations (from GenCC):

multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

CEP55 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 (MetaRNN=1.6668961E-6).

BP6

Variant 10-93519749-A-T is Benign according to our data. Variant chr10-93519749-A-T is described in ClinVar as Benign. ClinVar VariationId is 1209684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018131.5. 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
	CEP55	NM_018131.5	MANE Select	c.1133A>T	p.His378Leu	missense	Exon 8 of 9	NP_060601.4
	CEP55	NM_001127182.2		c.1133A>T	p.His378Leu	missense	Exon 8 of 9	NP_001120654.2	Q53EZ4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEP55	ENST00000371485.8	TSL:1 MANE Select	c.1133A>T	p.His378Leu	missense	Exon 8 of 9	ENSP00000360540.3	Q53EZ4-1
CEP55	ENST00000897343.1		c.1133A>T	p.His378Leu	missense	Exon 8 of 9	ENSP00000567402.1
CEP55	ENST00000912346.1		c.1133A>T	p.His378Leu	missense	Exon 8 of 9	ENSP00000582405.1

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96234

AN:

151984

Hom.:

33467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.691

Gnomad AMR

AF:

0.732

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.678

Gnomad FIN

AF:

0.807

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.766

Gnomad OTH

AF:

0.687

GnomAD2 exomes

AF:

0.714

AC:

179525

AN:

251300

AF XY:

0.722

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.757

Gnomad ASJ exome

AF:

0.761

Gnomad EAS exome

AF:

0.573

Gnomad FIN exome

AF:

0.799

Gnomad NFE exome

AF:

0.766

Gnomad OTH exome

AF:

0.737

GnomAD4 exome

AF:

0.740

AC:

1082179

AN:

1461646

Hom.:

405582

Cov.:

AF XY:

0.741

AC XY:

538712

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.301

AC:

10060

AN:

33476

American (AMR)

AF:

0.753

AC:

33690

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.761

AC:

19895

AN:

26132

East Asian (EAS)

AF:

0.556

AC:

22074

AN:

39690

South Asian (SAS)

AF:

0.693

AC:

59768

AN:

86256

European-Finnish (FIN)

AF:

0.798

AC:

42581

AN:

53384

Middle Eastern (MID)

AF:

0.714

AC:

4113

AN:

5764

European-Non Finnish (NFE)

AF:

0.762

AC:

847054

AN:

1111838

Other (OTH)

AF:

0.711

AC:

42944

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

14070

28139

42209

56278

70348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20232

40464

60696

80928

101160

<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:

0.633

AC:

96262

AN:

152102

Hom.:

33484

Cov.:

AF XY:

0.637

AC XY:

47354

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.321

AC:

13324

AN:

41476

American (AMR)

AF:

0.732

AC:

11204

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.761

AC:

2641

AN:

3470

East Asian (EAS)

AF:

0.566

AC:

2917

AN:

5150

South Asian (SAS)

AF:

0.677

AC:

3263

AN:

4818

European-Finnish (FIN)

AF:

0.807

AC:

8540

AN:

10584

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.766

AC:

52085

AN:

67988

Other (OTH)

AF:

0.690

AC:

1458

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1519

3038

4556

6075

7594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.738

Hom.:

29441

Bravo

AF:

0.610

TwinsUK

AF:

0.761

AC:

2822

ALSPAC

AF:

0.769

AC:

2964

ESP6500AA

AF:

0.328

AC:

1443

ESP6500EA

AF:

0.755

AC:

6494

ExAC

AF:

0.703

AC:

85369

Asia WGS

AF:

0.635

AC:

2208

AN:

3478

EpiCase

AF:

0.761

EpiControl

AF:

0.767

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CEP55-related disorder (1)

Multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.039

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0000017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

6.1

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.081

Sift

Benign

0.089

Sift4G

Uncertain

0.050

Polyphen

0.48

Vest4

0.18

MPC

0.25

ClinPred

0.026

GERP RS

5.8

Varity_R

0.099

gMVP

0.34

Mutation Taster

=92/8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over