10-5768316-C-G

Variant names:

• chr10-5768316-C-G
• NM_001494.4:c.888G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001494.4(GDI2):​c.888G>C​(p.Gln296His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GDI2 NM_001494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDI2	NM_001494.4	c.888G>C	p.Gln296His	missense_variant	Exon 8 of 11	ENST00000380191.9	NP_001485.2
GDI2	NM_001115156.2	c.753G>C	p.Gln251His	missense_variant	Exon 7 of 10		NP_001108628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDI2	ENST00000380191.9	c.888G>C	p.Gln296His	missense_variant	Exon 8 of 11	1	NM_001494.4	ENSP00000369538.4
GDI2	ENST00000380181.7	c.753G>C	p.Gln251His	missense_variant	Exon 7 of 10	1		ENSP00000369528.3
GDI2	ENST00000447751.5	c.372G>C	p.Gln124His	missense_variant	Exon 4 of 6	3		ENSP00000387565.1
GDI2	ENST00000479928.1	n.1074G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460354 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726638

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.888G>C (p.Q296H) alteration is located in exon 8 (coding exon 8) of the GDI2 gene. This alteration results from a G to C substitution at nucleotide position 888, causing the glutamine (Q) at amino acid position 296 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;D;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Uncertain	0.54
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.82	P;.;.
Vest4		0.35
MVP		0.71
MPC		0.34
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.34
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-5810279;