rs1129614

Positions:

• chr10-5766123-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001494.4(GDI2):​c.1221C>T​(p.Thr407=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,611,522 control chromosomes in the GnomAD database, including 32,951 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 0.17 (2457 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30494 hom.)
• Consequence: GDI2 NM_001494.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017267466).
• BP7: Synonymous conserved (PhyloP=-0.106 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDI2	NM_001494.4	c.1221C>T	p.Thr407=	synonymous_variant	11/11	ENST00000380191.9
GDI2	NM_001115156.2	c.1086C>T	p.Thr362=	synonymous_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDI2	ENST00000380191.9	c.1221C>T	p.Thr407=	synonymous_variant	11/11	1	NM_001494.4	P1
GDI2	ENST00000380181.7	c.1086C>T	p.Thr362=	synonymous_variant	10/10	1
GDI2	ENST00000447751.5	c.560C>T	p.Pro187Leu	missense_variant	6/6	3
GDI2	ENST00000479928.1	n.1605C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25708 AN: 152048 Hom.: 2454 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.186 AC: 46723 AN: 251142 Hom.: 4775 AF XY: 0.185 AC XY: 25103 AN XY: 135752

Gnomad AFR exome AF: 0.0706

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.152

Gnomad SAS exome AF: 0.119

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.200 AC: 292219 AN: 1459356 Hom.: 30494 Cov.: 30 AF XY: 0.198 AC XY: 143663 AN XY: 726118

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.237

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.169 AC: 25715 AN: 152166 Hom.: 2457 Cov.: 32 AF XY: 0.168 AC XY: 12491 AN XY: 74384

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.176

Alfa AF: 0.198 Hom.: 5257

Bravo AF: 0.169

TwinsUK AF: 0.207 AC: 768

ALSPAC AF: 0.211 AC: 813

ESP6500AA AF: 0.0772 AC: 340

ESP6500EA AF: 0.208 AC: 1791

ExAC AF: 0.181 AC: 22002

Asia WGS AF: 0.0980 AC: 339 AN: 3478

EpiCase AF: 0.206

EpiControl AF: 0.203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.89
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	7.7e-23	P;P;P
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.043
Sift	Benign	0.040	D
Sift4G	Uncertain	0.012	D
ClinPred		0.0019	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1129614; hg19: chr10-5808086; COSMIC: COSV60167543; COSMIC: COSV60167543;