10-5800591-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001494.4(GDI2):c.153+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000734 in 1,301,468 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (3 hom.)
• Consequence: GDI2 NM_001494.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002479
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.177

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-5800591-C-T is Benign according to our data. Variant chr10-5800591-C-T is described in ClinVar as [Benign]. Clinvar id is 769765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDI2	NM_001494.4	c.153+7G>A		splice_region_variant, intron_variant		ENST00000380191.9
GDI2	NM_001115156.2	c.153+7G>A		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDI2	ENST00000380191.9	c.153+7G>A		splice_region_variant, intron_variant		1	NM_001494.4	P1

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 520 AN: 152168 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.000880 AC: 221 AN: 251170 Hom.: 1 AF XY: 0.000567 AC XY: 77 AN XY: 135760

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000367 AC: 422 AN: 1149182 Hom.: 3 Cov.: 16 AF XY: 0.000271 AC XY: 159 AN XY: 586966

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.000969

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000625

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000133

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.00350 AC: 533 AN: 152286 Hom.: 3 Cov.: 32 AF XY: 0.00307 AC XY: 229 AN XY: 74476

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00369

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.69
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0
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: rs112406141; hg19: chr10-5842554;