chr2-65069146-T-C

Variant names:

• chr2-65069146-T-C
• rs2252867
• NM_015147.3:c.-46-253T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015147.3(CEP68):​c.-46-253T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,948 control chromosomes in the GnomAD database, including 12,494 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 0.40 (12494 hom., cov: 31)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015147.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	NM_015147.3	MANE Select	c.-46-253T>C		intron	N/A	NP_055962.2	Q76N32-1
	CEP68	NM_001319100.2		c.-46-253T>C		intron	N/A	NP_001306029.1	Q76N32-1
	CEP68	NM_001410838.1		c.-46-253T>C		intron	N/A	NP_001397767.1	A0A994J4E5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.-46-253T>C		intron	N/A	ENSP00000367229.2	Q76N32-1
	CEP68	ENST00000260569.4	TSL:1	c.-46-253T>C		intron	N/A	ENSP00000260569.4	Q76N32-2
	CEP68	ENST00000537589.1	TSL:1	n.74-2308T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60728 AN: 151828 Hom.: 12461 Cov.: 31

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.400 AC: 60810 AN: 151948 Hom.: 12494 Cov.: 31 AF XY: 0.398 AC XY: 29561 AN XY: 74272

African (AFR) AF: 0.473 AC: 19572 AN: 41418

American (AMR) AF: 0.367 AC: 5614 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3470

East Asian (EAS) AF: 0.334 AC: 1723 AN: 5154

South Asian (SAS) AF: 0.427 AC: 2059 AN: 4818

European-Finnish (FIN) AF: 0.319 AC: 3364 AN: 10556

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.373 AC: 25334 AN: 67936

Other (OTH) AF: 0.437 AC: 921 AN: 2106

Alfa AF: 0.395 Hom.: 2827

Bravo AF: 0.405

Asia WGS AF: 0.457 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.1
DANN	Benign	0.80
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2252867; hg19: chr2-65296280; COSMIC: COSV53127824; COSMIC: COSV53127824;