8-89924615-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001126111.3(OSGIN2):c.733G>A(p.Val245Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,613,686 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: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
OSGIN2
NM_001126111.3 missense
NM_001126111.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 4.19
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]
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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=0.051241934).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OSGIN2 | NM_001126111.3 | c.733G>A | p.Val245Ile | missense_variant | 6/6 | ENST00000451899.7 | NP_001119583.1 | |
OSGIN2 | NM_004337.2 | c.601G>A | p.Val201Ile | missense_variant | 6/6 | NP_004328.1 | ||
OSGIN2 | XM_011517287.4 | c.601G>A | p.Val201Ile | missense_variant | 6/6 | XP_011515589.1 | ||
OSGIN2 | XM_011517288.4 | c.202G>A | p.Val68Ile | missense_variant | 3/3 | XP_011515590.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OSGIN2 | ENST00000451899.7 | c.733G>A | p.Val245Ile | missense_variant | 6/6 | 1 | NM_001126111.3 | ENSP00000396445 | ||
OSGIN2 | ENST00000297438.6 | c.601G>A | p.Val201Ile | missense_variant | 6/6 | 1 | ENSP00000297438 | P1 | ||
OSGIN2 | ENST00000647849.1 | c.601G>A | p.Val201Ile | missense_variant | 6/6 | ENSP00000497119 | P1 | |||
NBN | ENST00000697292.1 | c.*765C>T | 3_prime_UTR_variant | 17/17 | ENSP00000513229 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152072Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 250980Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135640
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461496Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727080
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74398
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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 | Apr 25, 2022 | The c.733G>A (p.V245I) alteration is located in exon 6 (coding exon 6) of the OSGIN2 gene. This alteration results from a G to A substitution at nucleotide position 733, causing the valine (V) at amino acid position 245 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Benign
.;T;T
Sift4G
Benign
.;T;T
Polyphen
B;B;P
Vest4
0.086, 0.080
MVP
0.082
MPC
0.40
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at