chr2-65069473-C-T

Variant names:

• chr2-65069473-C-T
• rs368107291
• NM_015147.3:c.29C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_015147.3(CEP68):​c.29C>T​(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000921 in 1,519,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: CEP68 NM_015147.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.357
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016345471).
• BP6: Variant 2-65069473-C-T is Benign according to our data. Variant chr2-65069473-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3832039.Status of the report is criteria_provided_single_submitter, 1 stars.

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.29C>T	p.Ala10Val	missense	Exon 2 of 7	NP_055962.2	Q76N32-1
	CEP68	NM_001319100.2		c.29C>T	p.Ala10Val	missense	Exon 2 of 7	NP_001306029.1	Q76N32-1
	CEP68	NM_001410838.1		c.29C>T	p.Ala10Val	missense	Exon 2 of 6	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.29C>T	p.Ala10Val	missense	Exon 2 of 7	ENSP00000367229.2	Q76N32-1
	CEP68	ENST00000260569.4	TSL:1	c.29C>T	p.Ala10Val	missense	Exon 2 of 7	ENSP00000260569.4	Q76N32-2
	CEP68	ENST00000537589.1	TSL:1	n.74-1981C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000164 AC: 3 AN: 182630 AF XY: 0.0000207

Gnomad AFR exome AF: 0.0000653

Gnomad AMR exome AF: 0.0000454

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000619

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000512 AC: 7 AN: 1367158 Hom.: 0 Cov.: 30 AF XY: 0.00000747 AC XY: 5 AN XY: 669594

African (AFR) AF: 0.0000656 AC: 2 AN: 30484

American (AMR) AF: 0.0000329 AC: 1 AN: 30372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19998

East Asian (EAS) AF: 0.0000515 AC: 2 AN: 38810

South Asian (SAS) AF: 0.0000140 AC: 1 AN: 71210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5298

European-Non Finnish (NFE) AF: 9.39e-7 AC: 1 AN: 1064946

Other (OTH) AF: 0.00 AC: 0 AN: 56170

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74322

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.000327 AC: 5 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000833 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.4
DANN	Benign	0.82
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.83	N
PhyloP100		-0.36
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.0090
Sift	Benign	0.44	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.041
MVP		0.14
MPC		0.045
ClinPred		0.0037	T
GERP RS		-6.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.041
gMVP		0.046
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs368107291; hg19: chr2-65296607;