8-89924867-A-G

Variant summary

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

The NM_001126111.3(OSGIN2):ā€‹c.985A>Gā€‹(p.Met329Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 32)
Exomes š‘“: 0.000095 ( 0 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19
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]
NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.038650155).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSGIN2NM_001126111.3 linkuse as main transcriptc.985A>G p.Met329Val missense_variant 6/6 ENST00000451899.7 NP_001119583.1
OSGIN2NM_004337.2 linkuse as main transcriptc.853A>G p.Met285Val missense_variant 6/6 NP_004328.1
OSGIN2XM_011517287.4 linkuse as main transcriptc.853A>G p.Met285Val missense_variant 6/6 XP_011515589.1
OSGIN2XM_011517288.4 linkuse as main transcriptc.454A>G p.Met152Val missense_variant 3/3 XP_011515590.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSGIN2ENST00000451899.7 linkuse as main transcriptc.985A>G p.Met329Val missense_variant 6/61 NM_001126111.3 ENSP00000396445 Q9Y236-2
OSGIN2ENST00000297438.6 linkuse as main transcriptc.853A>G p.Met285Val missense_variant 6/61 ENSP00000297438 P1Q9Y236-1
OSGIN2ENST00000647849.1 linkuse as main transcriptc.853A>G p.Met285Val missense_variant 6/6 ENSP00000497119 P1Q9Y236-1
NBNENST00000697292.1 linkuse as main transcriptc.*513T>C 3_prime_UTR_variant 17/17 ENSP00000513229 P1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000135
AC:
34
AN:
251100
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135692
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.000878
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000951
AC:
139
AN:
1461866
Hom.:
0
Cov.:
32
AF XY:
0.0000908
AC XY:
66
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.000768
Gnomad4 NFE exome
AF:
0.0000809
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000160
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000988
AC:
12
EpiCase
AF:
0.000327
EpiControl
AF:
0.0000593

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 GeneticsAug 13, 2021The c.985A>G (p.M329V) alteration is located in exon 6 (coding exon 6) of the OSGIN2 gene. This alteration results from a A to G substitution at nucleotide position 985, causing the methionine (M) at amino acid position 329 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
0.068
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
9.8
DANN
Benign
0.90
DEOGEN2
Benign
0.033
T;T;.
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.36
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.78
.;T;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.039
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;N;.
MutationTaster
Benign
0.75
D;D
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.85
.;N;N
REVEL
Benign
0.091
Sift
Benign
0.23
.;T;T
Sift4G
Benign
0.30
.;T;T
Polyphen
0.0
B;B;B
Vest4
0.15, 0.15
MVP
0.27
MPC
0.35
ClinPred
0.019
T
GERP RS
1.8
Varity_R
0.057
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs202111827; hg19: chr8-90937095; COSMIC: COSV52409327; COSMIC: COSV52409327; API