chr2-65080227-C-G

Position:

• chr2-65080227-C-G

Variant summary

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

The ENST00000377990.7(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 ENST00000377990.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.2104+2263C>G		intron_variant		ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.2104+2263C>G		intron_variant		1	NM_015147.3	ENSP00000367229	P2

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

Gnomad4 AFR exome AF: 0.00609

Gnomad4 AMR exome AF: 0.0982

Gnomad4 ASJ exome AF: 0.0154

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.0130

Gnomad4 FIN exome AF: 0.0145

Gnomad4 NFE exome AF: 0.00453

Gnomad4 OTH exome AF: 0.0181

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

Gnomad4 AFR AF: 0.00901

Gnomad4 AMR AF: 0.0702

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.00538

Gnomad4 OTH AF: 0.0270

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.76

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: rs10519011; hg19: chr2-65307361;