8-89924933-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001126111.3(OSGIN2):​c.1051G>T​(p.Val351Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OSGIN2
NM_001126111.3 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91
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 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/exons MANE Protein UniProt
OSGIN2NM_001126111.3 linkuse as main transcriptc.1051G>T p.Val351Leu missense_variant 6/6 ENST00000451899.7 NP_001119583.1
OSGIN2NM_004337.2 linkuse as main transcriptc.919G>T p.Val307Leu missense_variant 6/6 NP_004328.1
OSGIN2XM_011517287.4 linkuse as main transcriptc.919G>T p.Val307Leu missense_variant 6/6 XP_011515589.1
OSGIN2XM_011517288.4 linkuse as main transcriptc.520G>T p.Val174Leu 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.1051G>T p.Val351Leu missense_variant 6/61 NM_001126111.3 ENSP00000396445 Q9Y236-2
OSGIN2ENST00000297438.6 linkuse as main transcriptc.919G>T p.Val307Leu missense_variant 6/61 ENSP00000297438 P1Q9Y236-1
OSGIN2ENST00000647849.1 linkuse as main transcriptc.919G>T p.Val307Leu missense_variant 6/6 ENSP00000497119 P1Q9Y236-1
NBNENST00000697292.1 linkuse as main transcriptc.*447C>A 3_prime_UTR_variant 17/17 ENSP00000513229 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 GeneticsJun 07, 2024The c.1051G>T (p.V351L) alteration is located in exon 6 (coding exon 6) of the OSGIN2 gene. This alteration results from a G to T substitution at nucleotide position 1051, causing the valine (V) at amino acid position 351 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
Pathogenic
0.57
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
T;T;.
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
.;T;T
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Pathogenic
3.0
M;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-2.3
.;N;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.020
.;D;D
Sift4G
Uncertain
0.011
.;D;D
Polyphen
0.96
D;D;D
Vest4
0.53, 0.53
MutPred
0.60
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;
MVP
0.46
MPC
0.69
ClinPred
0.98
D
GERP RS
4.6
Varity_R
0.20
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-90937161; API