rs61903295

chr11-95821969-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_014679.5(CEP57):c.798A>G(p.Pro266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 1,610,584 control chromosomes in the GnomAD database, including 1,024 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. P266P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.029 (87 hom., cov: 32)
  • Exomes 𝑓: 0.033 (937 hom.)
• Consequence: CEP57 NM_014679.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 11-95821969-A-G is Benign according to our data. Variant chr11-95821969-A-G is described in ClinVar as [Benign]. Clinvar id is 414983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.79 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP57	NM_014679.5	c.798A>G	p.Pro266=	synonymous_variant	7/11	ENST00000325542.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP57	ENST00000325542.10	c.798A>G	p.Pro266=	synonymous_variant	7/11	1	NM_014679.5

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4411 AN: 152118 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.00937

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0486

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0415

GnomAD3 exomes AF: 0.0324 AC: 8079 AN: 249316 Hom.: 160 AF XY: 0.0328 AC XY: 4425 AN XY: 134896

Gnomad AFR exome AF: 0.00728

Gnomad AMR exome AF: 0.0248

Gnomad ASJ exome AF: 0.0646

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.0156

Gnomad FIN exome AF: 0.0493

Gnomad NFE exome AF: 0.0414

Gnomad OTH exome AF: 0.0439

GnomAD4 exome AF: 0.0332 AC: 48485 AN: 1458348 Hom.: 937 Cov.: 30 AF XY: 0.0333 AC XY: 24138 AN XY: 725632

Gnomad4 AFR exome AF: 0.00856

Gnomad4 AMR exome AF: 0.0256

Gnomad4 ASJ exome AF: 0.0674

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.0519

Gnomad4 NFE exome AF: 0.0348

Gnomad4 OTH exome AF: 0.0361

GnomAD4 genome AF: 0.0290 AC: 4414 AN: 152236 Hom.: 87 Cov.: 32 AF XY: 0.0293 AC XY: 2184 AN XY: 74438

Gnomad4 AFR AF: 0.00936

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0486

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0411

Alfa AF: 0.0359 Hom.: 62

Bravo AF: 0.0272

Asia WGS AF: 0.0100 AC: 35 AN: 3478

EpiCase AF: 0.0417

EpiControl AF: 0.0442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mosaic variegated aneuploidy syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	10
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs61903295; hg19: chr11-95555133;