Genetic Variant OCIAD2:p.Gly68Glu (chr4-48897818-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001014446.3(OCIAD2):c.203G>A(p.Gly68Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000869 in 1,611,370 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

OCIAD2
NM_001014446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89

Variant links:

Genes affected

OCIAD2 (HGNC:28685): (OCIA domain containing 2) Predicted to be involved in endocytosis; hematopoietic stem cell homeostasis; and positive regulation of receptor signaling pathway via JAK-STAT. Predicted to act upstream of or within response to bacterium. Predicted to be located in Golgi apparatus; endosome; and lysosome. [provided by Alliance of Genome Resources, Apr 2022]

OCIAD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
OCIAD2	NM_001014446.3 link	c.203G>A	p.Gly68Glu	missense_variant	Exon 4 of 7	ENST00000508632.6	NP_001014446.1	Q56VL3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OCIAD2	ENST00000508632.6 link	c.203G>A	p.Gly68Glu	missense_variant	Exon 4 of 7	1	NM_001014446.3	ENSP00000423014.1		Q56VL3-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251196

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000822

AC:

AN:

1459308

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.203G>A (p.G68E) alteration is located in exon 4 (coding exon 3) of the OCIAD2 gene. This alteration results from a G to A substitution at nucleotide position 203, causing the glycine (G) at amino acid position 68 to be replaced by a glutamic acid (E). 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

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;.;.;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

T;.;T;T

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

M;M;M;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-4.4

D;D;.;D

REVEL

Uncertain

0.29

Sift

Benign

0.035

D;D;.;D

Sift4G

Uncertain

0.0050

D;D;D;.

Polyphen

1.0

D;D;D;.

Vest4

0.88

MutPred

0.66

Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);Gain of solvent accessibility (P = 0.1045);

MVP

0.52

MPC

0.48

ClinPred

0.91

GERP RS

5.1

Varity_R

0.63

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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