8-60610351-C-T

Position:

• chr8-60610351-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002865.3(RAB2A):​c.475-8229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,094 control chromosomes in the GnomAD database, including 24,522 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 0.53 (24522 hom., cov: 32)
• Consequence: RAB2A NM_002865.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

Genes affected

RAB2A (HGNC:9763): (RAB2A, member RAS oncogene family) The protein encoded by this gene belongs to the Rab family, members of which are small molecular weight guanosine triphosphatases (GTPases) that contain highly conserved domains involved in GTP binding and hydrolysis. The Rabs are membrane-bound proteins, involved in vesicular fusion and trafficking. This protein is a resident of pre-Golgi intermediates, and is required for protein transport from the endoplasmic reticulum (ER) to the Golgi complex. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB2A	NM_002865.3	c.475-8229C>T		intron_variant		ENST00000262646.12	NP_002856.1
RAB2A	NM_001242644.1	c.403-8229C>T		intron_variant			NP_001229573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB2A	ENST00000262646.12	c.475-8229C>T		intron_variant		1	NM_002865.3	ENSP00000262646	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81025 AN: 151976 Hom.: 24473 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.533 AC: 81138 AN: 152094 Hom.: 24522 Cov.: 32 AF XY: 0.536 AC XY: 39844 AN XY: 74340

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.621

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.530

Alfa AF: 0.380 Hom.: 2087

Bravo AF: 0.542

Asia WGS AF: 0.649 AC: 2258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs595255; hg19: chr8-61522910;