rs2723087

Variant names:

• chr2-65071148-T-A
• rs2723087
• NM_015147.3:c.358-306T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-65071148-T-A
• chr2-65071148-T-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.358-306T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 396,542 control chromosomes in the GnomAD database, including 28,191 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 0.38 (11317 hom., cov: 31)
  • Exomes 𝑓: 0.36 (16874 hom.)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3	c.358-306T>A		intron_variant	Intron 2 of 6	ENST00000377990.7	NP_055962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.358-306T>A		intron_variant	Intron 2 of 6	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57719 AN: 151848 Hom.: 11289 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.364 AC: 88906 AN: 244576 Hom.: 16874 Cov.: 0 AF XY: 0.368 AC XY: 47293 AN XY: 128676

African (AFR) AF: 0.470 AC: 3584 AN: 7622

American (AMR) AF: 0.340 AC: 2886 AN: 8484

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 3668 AN: 7630

East Asian (EAS) AF: 0.319 AC: 4735 AN: 14830

South Asian (SAS) AF: 0.423 AC: 11954 AN: 28276

European-Finnish (FIN) AF: 0.303 AC: 4232 AN: 13984

Middle Eastern (MID) AF: 0.422 AC: 468 AN: 1110

European-Non Finnish (NFE) AF: 0.350 AC: 51892 AN: 148252

Other (OTH) AF: 0.381 AC: 5487 AN: 14388

GnomAD4 genome AF: 0.380 AC: 57796 AN: 151966 Hom.: 11317 Cov.: 31 AF XY: 0.379 AC XY: 28135 AN XY: 74274

African (AFR) AF: 0.461 AC: 19091 AN: 41410

American (AMR) AF: 0.351 AC: 5361 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1722 AN: 5154

South Asian (SAS) AF: 0.412 AC: 1987 AN: 4822

European-Finnish (FIN) AF: 0.305 AC: 3216 AN: 10558

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23505 AN: 67964

Other (OTH) AF: 0.417 AC: 880 AN: 2108

Alfa AF: 0.365 Hom.: 1260

Bravo AF: 0.386

Asia WGS AF: 0.451 AC: 1569 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	3.8
DANN	Benign	0.62
PhyloP100		0.087
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: rs2723087; hg19: chr2-65298282;