chr2-65067398-T-C

Variant names:

• chr2-65067398-T-C
• rs6546122
• NM_015147.3:c.-46-2001T>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.-46-2001T>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
• Publications: 1 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=-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 rank	MANE	Protein	UniProt
CEP68	NM_015147.3	c.-46-2001T>C		intron_variant	Intron 1 of 6	ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.-46-2001T>C		intron_variant	Intron 1 of 6	1	NM_015147.3	ENSP00000367229.2

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

African (AFR) AF: 0.0257 AC: 1061 AN: 41206

American (AMR) AF: 0.0610 AC: 929 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3470

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5130

South Asian (SAS) AF: 0.0144 AC: 69 AN: 4788

European-Finnish (FIN) AF: 0.0961 AC: 1011 AN: 10520

Middle Eastern (MID) AF: 0.0655 AC: 19 AN: 290

European-Non Finnish (NFE) AF: 0.0999 AC: 6783 AN: 67890

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

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
PhyloP100		-4.3
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: rs6546122; hg19: chr2-65294532;