2-65071698-CC-GT

Variant names:

• chr2-65071698-CC-GT
• NM_015147.3:c.602_603delCCinsGT
• CEP68 p.Ser201Cys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015147.3(CEP68):​c.602_603delCCinsGT​(p.Ser201Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEP68 NM_015147.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04
• Publications: 0 publications found

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB1A (HGNC:9758): (RAB1A, member RAS oncogene family) This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]

RAB1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015147.3. 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
	CEP68	NM_015147.3	MANE Select	c.602_603delCCinsGT	p.Ser201Cys	missense	N/A	NP_055962.2	Q76N32-1
	CEP68	NM_001319100.2		c.602_603delCCinsGT	p.Ser201Cys	missense	N/A	NP_001306029.1	Q76N32-1
	CEP68	NM_001410838.1		c.602_603delCCinsGT	p.Ser201Cys	missense	N/A	NP_001397767.1	A0A994J4E5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.602_603delCCinsGT	p.Ser201Cys	missense	N/A	ENSP00000367229.2	Q76N32-1
	CEP68	ENST00000260569.4	TSL:1	c.602_603delCCinsGT	p.Ser201Cys	missense	N/A	ENSP00000260569.4	Q76N32-2
	CEP68	ENST00000537589.1	TSL:1	n.318_319delCCinsGT		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-65298832;