Variant chr10-5785253-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001494.4(GDI2):c.608A>G(p.Tyr203Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,450,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GDI2
NM_001494.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.19

Variant links:

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]

GDI2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.078983635).

BP6

Variant 10-5785253-T-C is Benign according to our data. Variant chr10-5785253-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2491034.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDI2	NM_001494.4 linkuse as main transcript	c.608A>G	p.Tyr203Cys	missense_variant	6/11	ENST00000380191.9	NP_001485.2	P50395-1Q6IAT1
GDI2	NM_001115156.2 linkuse as main transcript	c.473A>G	p.Tyr158Cys	missense_variant	5/10		NP_001108628.1	P50395-2Q6IAT1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GDI2	ENST00000380191.9 linkuse as main transcript	c.608A>G	p.Tyr203Cys	missense_variant	6/11	1	NM_001494.4	ENSP00000369538.4	P50395-1
GDI2	ENST00000380181.7 linkuse as main transcript	c.473A>G	p.Tyr158Cys	missense_variant	5/10	1		ENSP00000369528.3	P50395-2
GDI2	ENST00000456041.5 linkuse as main transcript	c.578A>G	p.Tyr193Cys	missense_variant	6/7	5		ENSP00000401733.1	Q5SX87
GDI2	ENST00000447751.5 linkuse as main transcript	c.92A>G	p.Tyr31Cys	missense_variant	2/6	3		ENSP00000387565.1	Q5SX91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250050

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135228

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1450144

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.41

T;T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.37

T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.079

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.26

N;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.040

N;N;N;N

REVEL

Benign

0.051

Sift

Benign

0.25

T;T;T;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.15

MVP

0.23

MPC

0.42

ClinPred

0.028

GERP RS

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over