2-65071705-A-G

Variant names:

• chr2-65071705-A-G
• rs17849707
• NM_015147.3:c.609A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015147.3(CEP68):​c.609A>G​(p.Thr203Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,613,838 control chromosomes in the GnomAD database, including 43,362 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 (3873 hom., cov: 31)
  • Exomes 𝑓: 0.23 (39489 hom.)
• Consequence: CEP68 NM_015147.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• 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]

RAB1A (HGNC:9758): (RAB1A, member RAS oncogene family) This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]

RAB1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-2.55 with no splicing effect.
• 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.609A>G	p.Thr203Thr	synonymous	Exon 3 of 7	NP_055962.2
	CEP68	NM_001319100.2		c.609A>G	p.Thr203Thr	synonymous	Exon 3 of 7	NP_001306029.1
	CEP68	NM_001410838.1		c.609A>G	p.Thr203Thr	synonymous	Exon 3 of 6	NP_001397767.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.609A>G	p.Thr203Thr	synonymous	Exon 3 of 7	ENSP00000367229.2
	CEP68	ENST00000260569.4	TSL:1	c.609A>G	p.Thr203Thr	synonymous	Exon 3 of 7	ENSP00000260569.4
	CEP68	ENST00000537589.1	TSL:1	n.325A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33155 AN: 151958 Hom.: 3859 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.247 AC: 62021 AN: 250818 AF XY: 0.252

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.321

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.228

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.227 AC: 332431 AN: 1461762 Hom.: 39489 Cov.: 50 AF XY: 0.231 AC XY: 167817 AN XY: 727186

African (AFR) AF: 0.174 AC: 5814 AN: 33480

American (AMR) AF: 0.247 AC: 11034 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 9505 AN: 26136

East Asian (EAS) AF: 0.319 AC: 12671 AN: 39698

South Asian (SAS) AF: 0.305 AC: 26349 AN: 86258

European-Finnish (FIN) AF: 0.204 AC: 10876 AN: 53326

Middle Eastern (MID) AF: 0.338 AC: 1952 AN: 5768

European-Non Finnish (NFE) AF: 0.215 AC: 239090 AN: 1111988

Other (OTH) AF: 0.251 AC: 15140 AN: 60394

GnomAD4 genome AF: 0.218 AC: 33204 AN: 152076 Hom.: 3873 Cov.: 31 AF XY: 0.220 AC XY: 16313 AN XY: 74314

African (AFR) AF: 0.169 AC: 7015 AN: 41492

American (AMR) AF: 0.241 AC: 3690 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1232 AN: 3464

East Asian (EAS) AF: 0.334 AC: 1718 AN: 5148

South Asian (SAS) AF: 0.306 AC: 1476 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2080 AN: 10582

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

European-Non Finnish (NFE) AF: 0.223 AC: 15130 AN: 67968

Other (OTH) AF: 0.258 AC: 545 AN: 2114

Alfa AF: 0.229 Hom.: 6475

Bravo AF: 0.221

Asia WGS AF: 0.377 AC: 1311 AN: 3478

EpiCase AF: 0.233

EpiControl AF: 0.234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.047
DANN	Benign	0.43
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs17849707; hg19: chr2-65298839; COSMIC: COSV53126743;