rs181776180

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014679.5(CEP57):​c.807+3G>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 0.0013 in 1,604,918 control chromosomes in the GnomAD database, including 31 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 0.0067 ( 15 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 16 hom. )

Consequence

CEP57
NM_014679.5 splice_region, intron

Scores

2
Splicing: ADA: 0.00003778
2

Clinical Significance

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

Conservation

PhyloP100: 2.22
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 11-95821981-G-A is Benign according to our data. Variant chr11-95821981-G-A is described in ClinVar as [Benign]. Clinvar id is 240922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-95821981-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00667 (1016/152284) while in subpopulation AFR AF= 0.023 (957/41570). AF 95% confidence interval is 0.0218. There are 15 homozygotes in gnomad4. There are 488 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CEP57NM_014679.5 linkuse as main transcriptc.807+3G>A splice_region_variant, intron_variant ENST00000325542.10 NP_055494.2 Q86XR8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CEP57ENST00000325542.10 linkuse as main transcriptc.807+3G>A splice_region_variant, intron_variant 1 NM_014679.5 ENSP00000317902.5 Q86XR8-1

Frequencies

GnomAD3 genomes
AF:
0.00668
AC:
1017
AN:
152166
Hom.:
15
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0231
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00275
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00176
AC:
437
AN:
248090
Hom.:
7
AF XY:
0.00124
AC XY:
167
AN XY:
134192
show subpopulations
Gnomad AFR exome
AF:
0.0226
Gnomad AMR exome
AF:
0.00152
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000161
Gnomad OTH exome
AF:
0.000992
GnomAD4 exome
AF:
0.000739
AC:
1074
AN:
1452634
Hom.:
16
Cov.:
27
AF XY:
0.000628
AC XY:
454
AN XY:
723008
show subpopulations
Gnomad4 AFR exome
AF:
0.0249
Gnomad4 AMR exome
AF:
0.00162
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000797
Gnomad4 OTH exome
AF:
0.00120
GnomAD4 genome
AF:
0.00667
AC:
1016
AN:
152284
Hom.:
15
Cov.:
32
AF XY:
0.00655
AC XY:
488
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0230
Gnomad4 AMR
AF:
0.00275
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00300
Hom.:
0
Bravo
AF:
0.00729
Asia WGS
AF:
0.000577
AC:
2
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
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 27, 2024- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
CADD
Benign
12
DANN
Benign
0.66
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000038
dbscSNV1_RF
Benign
0.084
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs181776180; hg19: chr11-95555145; API