Variant 4-48904530-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001014446.3(OCIAD2):c.20G>T(p.Arg7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

OCIAD2
NM_001014446.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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 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=0.06527704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OCIAD2	NM_001014446.3 linkuse as main transcript	c.20G>T	p.Arg7Leu	missense_variant	2/7	ENST00000508632.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OCIAD2	ENST00000508632.6 linkuse as main transcript	c.20G>T	p.Arg7Leu	missense_variant	2/7	1	NM_001014446.3	P1	Q56VL3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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: 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

Dec 21, 2022

The c.20G>T (p.R7L) alteration is located in exon 2 (coding exon 1) of the OCIAD2 gene. This alteration results from a G to T substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a leucine (L). 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

0.092

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.5

DANN

Benign

0.66

DEOGEN2

Benign

0.012

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.69

T;.;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.97

N;N;.;N

REVEL

Benign

0.062

Sift

Benign

0.13

T;T;.;T

Sift4G

Benign

0.46

T;T;T;.

Polyphen

0.18

B;B;B;.

Vest4

0.32

MutPred

0.35

Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);Loss of solvent accessibility (P = 0.0052);

MVP

0.061

MPC

0.091

ClinPred

0.042

GERP RS

1.6

Varity_R

0.085

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over