2-65082089-A-C

Variant names:

• chr2-65082089-A-C
• rs6546125
• NM_015147.3:c.2105-447A>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.2105-447A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,174 control chromosomes in the GnomAD database, including 2,795 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 0.18 (2795 hom., cov: 33)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.322 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.2105-447A>C		intron	N/A	NP_055962.2
	CEP68	NM_001319100.2		c.2105-447A>C		intron	N/A	NP_001306029.1
	CEP68	NM_001319101.2		c.1694-447A>C		intron	N/A	NP_001306030.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.2105-447A>C		intron	N/A	ENSP00000367229.2
	CEP68	ENST00000260569.4	TSL:1	c.1694-447A>C		intron	N/A	ENSP00000260569.4
	CEP68	ENST00000704486.1		c.2105-453A>C		intron	N/A	ENSP00000515914.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27374 AN: 152056 Hom.: 2781 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.180 AC: 27407 AN: 152174 Hom.: 2795 Cov.: 33 AF XY: 0.182 AC XY: 13556 AN XY: 74396

African (AFR) AF: 0.113 AC: 4687 AN: 41522

American (AMR) AF: 0.216 AC: 3305 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3472

East Asian (EAS) AF: 0.335 AC: 1731 AN: 5168

South Asian (SAS) AF: 0.289 AC: 1395 AN: 4830

European-Finnish (FIN) AF: 0.179 AC: 1898 AN: 10580

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12638 AN: 68000

Other (OTH) AF: 0.218 AC: 460 AN: 2112

Alfa AF: 0.193 Hom.: 3956

Bravo AF: 0.181

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.40
PhyloP100		2.5
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: rs6546125; hg19: chr2-65309223;