chr8-89924836-A-C

Variant summary

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

The NM_001126111.3(OSGIN2):ā€‹c.954A>Cā€‹(p.Glu318Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,052 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.00013 ( 0 hom., cov: 32)
Exomes š‘“: 0.00013 ( 1 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72
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=0.016717881).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSGIN2NM_001126111.3 linkuse as main transcriptc.954A>C p.Glu318Asp missense_variant 6/6 ENST00000451899.7 NP_001119583.1
OSGIN2NM_004337.2 linkuse as main transcriptc.822A>C p.Glu274Asp missense_variant 6/6 NP_004328.1
OSGIN2XM_011517287.4 linkuse as main transcriptc.822A>C p.Glu274Asp missense_variant 6/6 XP_011515589.1
OSGIN2XM_011517288.4 linkuse as main transcriptc.423A>C p.Glu141Asp 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.954A>C p.Glu318Asp missense_variant 6/61 NM_001126111.3 ENSP00000396445 Q9Y236-2
OSGIN2ENST00000297438.6 linkuse as main transcriptc.822A>C p.Glu274Asp missense_variant 6/61 ENSP00000297438 P1Q9Y236-1
OSGIN2ENST00000647849.1 linkuse as main transcriptc.822A>C p.Glu274Asp missense_variant 6/6 ENSP00000497119 P1Q9Y236-1
NBNENST00000697292.1 linkuse as main transcriptc.*544T>G 3_prime_UTR_variant 17/17 ENSP00000513229 P1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
251074
Hom.:
1
AF XY:
0.000214
AC XY:
29
AN XY:
135680
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00357
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000794
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000131
AC:
191
AN:
1461860
Hom.:
1
Cov.:
32
AF XY:
0.000144
AC XY:
105
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00406
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000540
Gnomad4 OTH exome
AF:
0.000315
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152192
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.000195
Hom.:
0
Bravo
AF:
0.000196
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000148
AC:
18
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 GeneticsDec 19, 2022The c.954A>C (p.E318D) alteration is located in exon 6 (coding exon 6) of the OSGIN2 gene. This alteration results from a A to C substitution at nucleotide position 954, causing the glutamic acid (E) at amino acid position 318 to be replaced by an aspartic acid (D). 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
0.10
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.051
T;T;.
Eigen
Benign
-0.12
Eigen_PC
Benign
0.022
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.61
.;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.017
T;T;T
MetaSVM
Benign
-0.69
T
MutationAssessor
Uncertain
2.0
M;M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.89
.;N;N
REVEL
Benign
0.17
Sift
Benign
0.20
.;T;T
Sift4G
Benign
0.28
.;T;T
Polyphen
0.034
B;B;B
Vest4
0.12, 0.13
MutPred
0.50
Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);.;
MVP
0.49
MPC
0.34
ClinPred
0.032
T
GERP RS
4.3
Varity_R
0.13
gMVP
0.53

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: rs200077072; hg19: chr8-90937064; API