rs2723087

Positions:

• chr2-65071148-T-A
• chr2-65071148-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015147.3(CEP68):​c.358-306T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 396,542 control chromosomes in the GnomAD database, including 28,191 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 0.38 (11317 hom., cov: 31)
  • Exomes 𝑓: 0.36 (16874 hom.)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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]

CEP68 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.358-306T>A		intron_variant		ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.358-306T>A		intron_variant		1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57719 AN: 151848 Hom.: 11289 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.364 AC: 88906 AN: 244576 Hom.: 16874 Cov.: 0 AF XY: 0.368 AC XY: 47293 AN XY: 128676

Gnomad4 AFR exome AF: 0.470

Gnomad4 AMR exome AF: 0.340

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.380 AC: 57796 AN: 151966 Hom.: 11317 Cov.: 31 AF XY: 0.379 AC XY: 28135 AN XY: 74274

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.417

Alfa AF: 0.365 Hom.: 1260

Bravo AF: 0.386

Asia WGS AF: 0.451 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
DANN	Benign	0.62

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: rs2723087; hg19: chr2-65298282;