Variant 4-48894042-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001014446.3(OCIAD2):c.229G>C(p.Ala77Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000297 in 1,347,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

OCIAD2
NM_001014446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.121

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.089957684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCIAD2	NM_001014446.3 linkuse as main transcript	c.229G>C	p.Ala77Pro	missense_variant	5/7	ENST00000508632.6	NP_001014446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OCIAD2	ENST00000508632.6 linkuse as main transcript	c.229G>C	p.Ala77Pro	missense_variant	5/7	1	NM_001014446.3	ENSP00000423014	P1	Q56VL3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000297

AC:

AN:

1347980

Hom.:

Cov.:

AF XY:

0.00000449

AC XY:

AN XY:

668624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000327

Gnomad4 AMR exome

AF:

0.00

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:

0.00000286

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2022

The c.229G>C (p.A77P) alteration is located in exon 5 (coding exon 4) of the OCIAD2 gene. This alteration results from a G to C substitution at nucleotide position 229, causing the alanine (A) at amino acid position 77 to be replaced by a proline (P). 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

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

T;.;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.77

T;.;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.090

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;N;N;.

MutationTaster

Benign

0.83

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.58

N;N;.;N

REVEL

Benign

0.042

Sift

Benign

0.40

T;T;.;T

Sift4G

Benign

0.25

T;T;T;.

Polyphen

0.0010

B;B;B;.

Vest4

0.30

MutPred

0.32

Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);

MVP

0.15

MPC

0.097

ClinPred

0.069

GERP RS

0.39

Varity_R

0.042

gMVP

0.57

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