2-65065436-G-T

Position:

• chr2-65065436-G-T

Variant summary

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

The NM_015147.3(CEP68):​c.-46-3963G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,148 control chromosomes in the GnomAD database, including 3,919 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 0.22 (3919 hom., cov: 32)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP68	NM_015147.3	c.-46-3963G>T		intron_variant		ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.-46-3963G>T		intron_variant		1	NM_015147.3	ENSP00000367229	P2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33430 AN: 152028 Hom.: 3904 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.220 AC: 33476 AN: 152148 Hom.: 3919 Cov.: 32 AF XY: 0.221 AC XY: 16452 AN XY: 74370

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.261

Alfa AF: 0.230 Hom.: 516

Bravo AF: 0.223

Asia WGS AF: 0.375 AC: 1303 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	0.61
DANN	Benign	0.59

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: rs2901749; hg19: chr2-65292570;