rs2497

Positions:

• chr10-5765645-A-G
• chr10-5765645-A-T

Variant summary

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

The NM_001494.4(GDI2):​c.*361T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 168,756 control chromosomes in the GnomAD database, including 10,595 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 0.35 (9392 hom., cov: 31)
  • Exomes 𝑓: 0.36 (1203 hom.)
• Consequence: GDI2 NM_001494.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

Genes affected

GDI2 (HGNC:4227): (GDP dissociation inhibitor 2) GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI2 is ubiquitously expressed. The GDI2 gene contains many repetitive elements indicating that it may be prone to inversion/deletion rearrangements. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDI2	NM_001494.4	c.*361T>C		3_prime_UTR_variant	11/11	ENST00000380191.9	NP_001485.2
GDI2	NM_001115156.2	c.*361T>C		3_prime_UTR_variant	10/10		NP_001108628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDI2	ENST00000380191	c.*361T>C		3_prime_UTR_variant	11/11	1	NM_001494.4	ENSP00000369538.4
GDI2	ENST00000479928.1	n.2083T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52496 AN: 151916 Hom.: 9380 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.359 AC: 5999 AN: 16720 Hom.: 1203 Cov.: 0 AF XY: 0.361 AC XY: 3161 AN XY: 8760

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.368

GnomAD4 genome AF: 0.346 AC: 52538 AN: 152036 Hom.: 9392 Cov.: 31 AF XY: 0.344 AC XY: 25537 AN XY: 74336

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.362

Alfa AF: 0.379 Hom.: 2263

Bravo AF: 0.343

Asia WGS AF: 0.334 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2497; hg19: chr10-5807608;