2-65067398-T-C

Variant summary

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

The NM_015147.3(CEP68):c.-46-2001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 151,532 control chromosomes in the GnomAD database, including 480 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 0.069 (480 hom., cov: 30)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP68	NM_015147.3	c.-46-2001T>C		intron_variant		ENST00000377990.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP68	ENST00000377990.7	c.-46-2001T>C		intron_variant		1	NM_015147.3	P2

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10464 AN: 151412 Hom.: 480 Cov.: 30

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0144

Gnomad FIN AF: 0.0961

Gnomad MID AF: 0.0769

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.0723

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

GnomAD4 genome AF: 0.0690 AC: 10459 AN: 151532 Hom.: 480 Cov.: 30 AF XY: 0.0678 AC XY: 5013 AN XY: 73988

Gnomad4 AFR AF: 0.0257

Gnomad4 AMR AF: 0.0610

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0144

Gnomad4 FIN AF: 0.0961

Gnomad4 NFE AF: 0.0999

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0435 Hom.: 66

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.027
Dann	Benign	0.44

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: rs6546122; hg19: chr2-65294532;