chr10-5766123-G-A

Variant names:

• chr10-5766123-G-A
• rs1129614
• NM_001494.4:c.1221C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001494.4(GDI2):​c.1221C>T​(p.Thr407Thr) 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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GDI2	NM_001494.4	c.1221C>T	p.Thr407Thr	synonymous_variant	Exon 11 of 11	ENST00000380191.9	NP_001485.2
GDI2	NM_001115156.2	c.1086C>T	p.Thr362Thr	synonymous_variant	Exon 10 of 10		NP_001108628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDI2	ENST00000380191.9	c.1221C>T	p.Thr407Thr	synonymous_variant	Exon 11 of 11	1	NM_001494.4	ENSP00000369538.4
GDI2	ENST00000380181.8	c.1086C>T	p.Thr362Thr	synonymous_variant	Exon 10 of 10	1		ENSP00000369528.3
GDI2	ENST00000447751.5	c.560C>T	p.Pro187Leu	missense_variant	Exon 6 of 6	3		ENSP00000387565.1
GDI2	ENST00000479928.1	n.1605C>T		non_coding_transcript_exon_variant	Exon 3 of 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

GnomAD2 exomes AF: 0.186 AC: 46723 AN: 251142 AF XY: 0.185

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 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

African (AFR) AF: 0.0691 AC: 2308 AN: 33420

American (AMR) AF: 0.237 AC: 10603 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4143 AN: 26110

East Asian (EAS) AF: 0.153 AC: 6078 AN: 39692

South Asian (SAS) AF: 0.119 AC: 10258 AN: 86212

European-Finnish (FIN) AF: 0.209 AC: 11185 AN: 53418

Middle Eastern (MID) AF: 0.116 AC: 666 AN: 5760

European-Non Finnish (NFE) AF: 0.212 AC: 235779 AN: 1109788

Other (OTH) AF: 0.186 AC: 11199 AN: 60310

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

African (AFR) AF: 0.0751 AC: 3118 AN: 41540

American (AMR) AF: 0.225 AC: 3443 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3470

East Asian (EAS) AF: 0.151 AC: 785 AN: 5186

South Asian (SAS) AF: 0.116 AC: 558 AN: 4812

European-Finnish (FIN) AF: 0.209 AC: 2211 AN: 10566

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14474 AN: 67998

Other (OTH) AF: 0.176 AC: 372 AN: 2114

Alfa AF: 0.191 Hom.: 8186

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
AlphaMissense	Benign	0.19
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
PhyloP100		-0.11
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
Mutation Taster		=86/14	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: rs1129614; hg19: chr10-5808086; COSMIC: COSV60167543; COSMIC: COSV60167543;