rs11742

Positions:

• chr11-95821924-G-A
• chr11-95821924-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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 (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (100 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1670 hom.)
• Consequence: CEP57 NM_014679.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.896

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-95821924-G-A is Benign according to our data. Variant chr11-95821924-G-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
CEP57	NM_014679.5	c.753G>A	p.Pro251Pro	synonymous_variant	7/11	ENST00000325542.10	NP_055494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP57	ENST00000325542.10	c.753G>A	p.Pro251Pro	synonymous_variant	7/11	1	NM_014679.5	ENSP00000317902.5

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4942 AN: 151908 Hom.: 100 Cov.: 32

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

GnomAD3 exomes AF: 0.0321 AC: 8045 AN: 250484 Hom.: 162 AF XY: 0.0325 AC XY: 4407 AN XY: 135458

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 SAS exome AF: 0.00700

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.: 30 AF XY: 0.0439 AC XY: 31866 AN XY: 726352

Gnomad4 AFR exome AF: 0.00760

Gnomad4 AMR exome AF: 0.0235

Gnomad4 ASJ exome AF: 0.0679

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00781

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0513

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.0325 AC: 4939 AN: 152026 Hom.: 100 Cov.: 32 AF XY: 0.0312 AC XY: 2317 AN XY: 74312

Gnomad4 AFR AF: 0.00931

Gnomad4 AMR AF: 0.0335

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0436

Alfa AF: 0.0392 Hom.: 83

Bravo AF: 0.0321

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mosaic variegated aneuploidy syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.46
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: rs11742; hg19: chr11-95555088;