2-65065436-G-T

Variant names:

• chr2-65065436-G-T
• rs2901749
• NM_015147.3:c.-46-3963G>T

Variant summary

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

The NM_015147.3(CEP68):​c.-46-3963G>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
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	NM_015147.3	MANE Select	c.-46-3963G>T		intron	N/A	NP_055962.2
	CEP68	NM_001319100.2		c.-46-3963G>T		intron	N/A	NP_001306029.1
	CEP68	NM_001410838.1		c.-46-3963G>T		intron	N/A	NP_001397767.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.-46-3963G>T		intron	N/A	ENSP00000367229.2
	CEP68	ENST00000260569.4	TSL:1	c.-46-3963G>T		intron	N/A	ENSP00000260569.4
	CEP68	ENST00000537589.1	TSL:1	n.74-6018G>T		intron	N/A

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

African (AFR) AF: 0.175 AC: 7268 AN: 41514

American (AMR) AF: 0.242 AC: 3695 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3466

East Asian (EAS) AF: 0.334 AC: 1729 AN: 5178

South Asian (SAS) AF: 0.307 AC: 1480 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2082 AN: 10576

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15123 AN: 67998

Other (OTH) AF: 0.261 AC: 551 AN: 2108

Alfa AF: 0.228 Hom.: 526

Bravo AF: 0.223

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.61
DANN	Benign	0.59
PhyloP100		0.17
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: rs2901749; hg19: chr2-65292570;