NM_015147.3:c.2104+2263C>G

Variant names:

• chr2-65080227-C-G
• rs10519011
• NM_015147.3:c.2104+2263C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015147.3(CEP68):​c.2104+2263C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 984,638 control chromosomes in the GnomAD database, including 342 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (208 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (134 hom.)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	NM_015147.3	MANE Select	c.2104+2263C>G		intron	N/A	NP_055962.2
	CEP68	NM_001319100.2		c.2104+2263C>G		intron	N/A	NP_001306029.1
	CEP68	NM_001410838.1		c.2105-49C>G		intron	N/A	NP_001397767.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.2104+2263C>G		intron	N/A	ENSP00000367229.2
	CEP68	ENST00000260569.4	TSL:1	c.1693+2263C>G		intron	N/A	ENSP00000260569.4
	CEP68	ENST00000704486.1		c.2104+2263C>G		intron	N/A	ENSP00000515914.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3375 AN: 151942 Hom.: 206 Cov.: 32

Gnomad AFR AF: 0.00904

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0702

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00538

Gnomad OTH AF: 0.0259

GnomAD4 exome AF: 0.00625 AC: 5203 AN: 832588 Hom.: 134 Cov.: 28 AF XY: 0.00592 AC XY: 2278 AN XY: 384498

African (AFR) AF: 0.00609 AC: 96 AN: 15766

American (AMR) AF: 0.0982 AC: 96 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.0154 AC: 79 AN: 5142

East Asian (EAS) AF: 0.208 AC: 749 AN: 3604

South Asian (SAS) AF: 0.0130 AC: 213 AN: 16436

European-Finnish (FIN) AF: 0.0145 AC: 4 AN: 276

Middle Eastern (MID) AF: 0.0130 AC: 21 AN: 1620

European-Non Finnish (NFE) AF: 0.00453 AC: 3452 AN: 761504

Other (OTH) AF: 0.0181 AC: 493 AN: 27262

GnomAD4 genome AF: 0.0222 AC: 3376 AN: 152050 Hom.: 208 Cov.: 32 AF XY: 0.0244 AC XY: 1815 AN XY: 74310

African (AFR) AF: 0.00901 AC: 374 AN: 41506

American (AMR) AF: 0.0702 AC: 1073 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 56 AN: 3466

East Asian (EAS) AF: 0.228 AC: 1174 AN: 5160

South Asian (SAS) AF: 0.0212 AC: 102 AN: 4812

European-Finnish (FIN) AF: 0.0164 AC: 172 AN: 10514

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.00538 AC: 366 AN: 68002

Other (OTH) AF: 0.0270 AC: 57 AN: 2108

Alfa AF: 0.0149 Hom.: 8

Bravo AF: 0.0279

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.76
PhyloP100		-0.23
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: rs10519011; hg19: chr2-65307361;