rs11742

Variant names:

• chr11-95821924-G-A
• rs11742
• NM_014679.5:c.753G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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 (★★). 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.896
• Publications: 5 publications found

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]

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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014679.5. 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
	CEP57	NM_014679.5	MANE Select	c.753G>A	p.Pro251Pro	synonymous	Exon 7 of 11	NP_055494.2
	CEP57	NM_001243776.2		c.726G>A	p.Pro242Pro	synonymous	Exon 8 of 12	NP_001230705.1	Q86XR8-5
	CEP57	NM_001243777.2		c.753G>A	p.Pro251Pro	synonymous	Exon 7 of 10	NP_001230706.1	Q86XR8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP57	ENST00000325542.10	TSL:1 MANE Select	c.753G>A	p.Pro251Pro	synonymous	Exon 7 of 11	ENSP00000317902.5	Q86XR8-1
	CEP57	ENST00000325486.9	TSL:1	c.753G>A	p.Pro251Pro	synonymous	Exon 7 of 10	ENSP00000317487.5	Q86XR8-2
	CEP57	ENST00000538658.5	TSL:1	c.753G>A	p.Pro251Pro	synonymous	Exon 7 of 7	ENSP00000445706.1	Q86XR8-3

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

GnomAD2 exomes AF: 0.0321 AC: 8045 AN: 250484 AF XY: 0.0325

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

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: 1 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

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

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: 0 AN: 5170

South Asian (SAS) AF: 0.00540 AC: 26 AN: 4812

European-Finnish (FIN) AF: 0.0272 AC: 287 AN: 10558

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0492 AC: 3341 AN: 67968

Other (OTH) AF: 0.0436 AC: 92 AN: 2110

Alfa AF: 0.0380 Hom.: 103

Bravo AF: 0.0321

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Mosaic variegated aneuploidy syndrome 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
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)

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

Other links and lift over

dbSNP: rs11742; hg19: chr11-95555088;