8-89921104-A-G

Variant summary

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

The NM_001126111.3(OSGIN2):ā€‹c.553A>Gā€‹(p.Ile185Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000562 in 1,602,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000060 ( 0 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
Variant links:
Genes affected
OSGIN2 (HGNC:1355): (oxidative stress induced growth inhibitor family member 2) Predicted to enable growth factor activity. Predicted to be involved in negative regulation of cell growth. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21398893).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSGIN2NM_001126111.3 linkuse as main transcriptc.553A>G p.Ile185Val missense_variant 5/6 ENST00000451899.7 NP_001119583.1 Q9Y236-2
OSGIN2NM_004337.2 linkuse as main transcriptc.421A>G p.Ile141Val missense_variant 5/6 NP_004328.1 Q9Y236-1A0A024R9D5
OSGIN2XM_011517287.4 linkuse as main transcriptc.421A>G p.Ile141Val missense_variant 5/6 XP_011515589.1 Q9Y236-1A0A024R9D5
OSGIN2XM_011517288.4 linkuse as main transcriptc.22A>G p.Ile8Val missense_variant 2/3 XP_011515590.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSGIN2ENST00000451899.7 linkuse as main transcriptc.553A>G p.Ile185Val missense_variant 5/61 NM_001126111.3 ENSP00000396445.2 Q9Y236-2
OSGIN2ENST00000297438.6 linkuse as main transcriptc.421A>G p.Ile141Val missense_variant 5/61 ENSP00000297438.2 Q9Y236-1
OSGIN2ENST00000647849.1 linkuse as main transcriptc.421A>G p.Ile141Val missense_variant 5/6 ENSP00000497119.1 Q9Y236-1
OSGIN2ENST00000520659.1 linkuse as main transcriptc.553A>G p.Ile185Val missense_variant 5/52 ENSP00000431029.1 E5RJZ3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152132
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000489
AC:
12
AN:
245188
Hom.:
0
AF XY:
0.0000528
AC XY:
7
AN XY:
132542
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000558
Gnomad SAS exome
AF:
0.000208
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000446
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000600
AC:
87
AN:
1450150
Hom.:
0
Cov.:
27
AF XY:
0.0000679
AC XY:
49
AN XY:
721788
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:
0.000344
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000498
Gnomad4 OTH exome
AF:
0.0000501
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152250
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000501
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsNov 19, 2024The c.553A>G (p.I185V) alteration is located in exon 5 (coding exon 5) of the OSGIN2 gene. This alteration results from a A to G substitution at nucleotide position 553, causing the isoleucine (I) at amino acid position 185 to be replaced by a valine (V). 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
0.14
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.046
T;T;.;.
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.81
.;T;T;T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.21
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;M;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.88
.;N;N;N
REVEL
Benign
0.12
Sift
Uncertain
0.015
.;D;T;T
Sift4G
Benign
0.16
.;T;T;D
Polyphen
0.30
B;B;P;.
Vest4
0.27, 0.32, 0.33
MutPred
0.58
Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);.;.;
MVP
0.13
MPC
0.31
ClinPred
0.11
T
GERP RS
5.5
Varity_R
0.11
gMVP
0.43

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.

Other links and lift over

dbSNP: rs565813627; hg19: chr8-90933332; API