8-89925128-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001126111.3(OSGIN2):ā€‹c.1246T>Cā€‹(p.Leu416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00028 ( 0 hom., cov: 32)
Exomes š‘“: 0.000021 ( 0 hom. )

Consequence

OSGIN2
NM_001126111.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.398
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 -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 8-89925128-T-C is Benign according to our data. Variant chr8-89925128-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2658681.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.398 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSGIN2NM_001126111.3 linkuse as main transcriptc.1246T>C p.Leu416= synonymous_variant 6/6 ENST00000451899.7 NP_001119583.1
OSGIN2NM_004337.2 linkuse as main transcriptc.1114T>C p.Leu372= synonymous_variant 6/6 NP_004328.1
OSGIN2XM_011517287.4 linkuse as main transcriptc.1114T>C p.Leu372= synonymous_variant 6/6 XP_011515589.1
OSGIN2XM_011517288.4 linkuse as main transcriptc.715T>C p.Leu239= synonymous_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.1246T>C p.Leu416= synonymous_variant 6/61 NM_001126111.3 ENSP00000396445 Q9Y236-2
OSGIN2ENST00000297438.6 linkuse as main transcriptc.1114T>C p.Leu372= synonymous_variant 6/61 ENSP00000297438 P1Q9Y236-1
OSGIN2ENST00000647849.1 linkuse as main transcriptc.1114T>C p.Leu372= synonymous_variant 6/6 ENSP00000497119 P1Q9Y236-1
NBNENST00000697292.1 linkuse as main transcriptc.*252A>G 3_prime_UTR_variant 17/17 ENSP00000513229 P1

Frequencies

GnomAD3 genomes
AF:
0.000263
AC:
40
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000917
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000760
AC:
19
AN:
250130
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135502
show subpopulations
Gnomad AFR exome
AF:
0.000889
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461772
Hom.:
0
Cov.:
32
AF XY:
0.0000193
AC XY:
14
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.000657
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000276
AC:
42
AN:
152334
Hom.:
0
Cov.:
32
AF XY:
0.000322
AC XY:
24
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.000287
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2022OSGIN2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
3.3
DANN
Benign
0.60
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs150510939; hg19: chr8-90937356; API