chr4-48897818-C-T

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

2
11
6

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]

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
OCIAD2NM_001014446.3 linkc.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
OCIAD2ENST00000508632.6 linkc.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:
2
AN:
152062
Hom.:
0
Cov.:
32
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:
10
AN:
251196
Hom.:
0
AF XY:
0.0000295
AC XY:
4
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:
12
AN:
1459308
Hom.:
0
Cov.:
29
AF XY:
0.00000689
AC XY:
5
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:
2
AN:
152062
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
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:
2

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
T
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.069
T;.;.;.
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.84
T;.;T;T
M_CAP
Benign
0.025
D
MetaRNN
Uncertain
0.65
D;D;D;D
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.6
M;M;M;.
PrimateAI
Uncertain
0.72
T
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
D
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.

Other links and lift over

dbSNP: rs780578947; hg19: chr4-48899835; API