2-65082305-A-G

Variant names:

• chr2-65082305-A-G
• rs78945874
• NM_015147.3:c.2105-231A>G

Variant summary

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

The NM_015147.3(CEP68):​c.2105-231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,258 control chromosomes in the GnomAD database, including 1,109 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 0.10 (1109 hom., cov: 33)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3	c.2105-231A>G		intron_variant	Intron 5 of 6	ENST00000377990.7	NP_055962.2
CEP68	NM_001319100.2	c.2105-231A>G		intron_variant	Intron 5 of 6		NP_001306029.1
CEP68	NM_001319101.2	c.1694-231A>G		intron_variant	Intron 5 of 6		NP_001306030.1
CEP68	NR_134966.2	n.2167-231A>G		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.2105-231A>G		intron_variant	Intron 5 of 6	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15719 AN: 152140 Hom.: 1110 Cov.: 33

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.103 AC: 15723 AN: 152258 Hom.: 1109 Cov.: 33 AF XY: 0.104 AC XY: 7779 AN XY: 74442

African (AFR) AF: 0.0239 AC: 994 AN: 41566

American (AMR) AF: 0.101 AC: 1540 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3472

East Asian (EAS) AF: 0.102 AC: 527 AN: 5186

South Asian (SAS) AF: 0.195 AC: 941 AN: 4828

European-Finnish (FIN) AF: 0.144 AC: 1523 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9091 AN: 68002

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.126 Hom.: 172

Bravo AF: 0.0956

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		0.49
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: rs78945874; hg19: chr2-65309439;