chr2-65083897-A-G

Variant names:

• chr2-65083897-A-G
• rs1050675
• NM_015147.3:c.*263A>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.*263A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,164 control chromosomes in the GnomAD database, including 2,058 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 0.16 (2058 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CEP68 NM_015147.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 12 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3	c.*263A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000377990.7	NP_055962.2
CEP68	NR_134966.2	n.2599A>G		non_coding_transcript_exon_variant	Exon 6 of 6
CEP68	NM_001319100.2	c.*263A>G		3_prime_UTR_variant	Exon 7 of 7		NP_001306029.1
CEP68	NM_001319101.2	c.*263A>G		3_prime_UTR_variant	Exon 7 of 7		NP_001306030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.*263A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24070 AN: 152044 Hom.: 2055 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.158 AC: 24102 AN: 152162 Hom.: 2058 Cov.: 32 AF XY: 0.158 AC XY: 11773 AN XY: 74390

African (AFR) AF: 0.214 AC: 8868 AN: 41500

American (AMR) AF: 0.124 AC: 1892 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3470

East Asian (EAS) AF: 0.102 AC: 527 AN: 5182

South Asian (SAS) AF: 0.196 AC: 946 AN: 4828

European-Finnish (FIN) AF: 0.143 AC: 1516 AN: 10598

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9149 AN: 67990

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.148 Hom.: 1117

Bravo AF: 0.158

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.53
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: rs1050675; hg19: chr2-65311031;