2-65079771-C-T

Position:

• chr2-65079771-C-T

Variant summary

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

The NM_015147.3(CEP68):​c.2104+1807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 152,156 control chromosomes in the GnomAD database, including 32,737 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 0.65 (32737 hom., cov: 33)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP68	NM_015147.3	c.2104+1807C>T		intron_variant		ENST00000377990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP68	ENST00000377990.7	c.2104+1807C>T		intron_variant		1	NM_015147.3	P2

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99343 AN: 152038 Hom.: 32723 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.653 AC: 99392 AN: 152156 Hom.: 32737 Cov.: 33 AF XY: 0.654 AC XY: 48643 AN XY: 74392

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.621

Alfa AF: 0.669 Hom.: 4213

Bravo AF: 0.648

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.078
DANN	Benign	0.43

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: rs6741255; hg19: chr2-65306905;