8-89924970-G-C

Position:

chr8-89924970-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001126111.3(OSGIN2):c.1088G>C(p.Cys363Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00215 in 1,613,886 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 36 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 46 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.78

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]

OSGIN2 links:

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]

NBN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008452892).

BP6

Variant 8-89924970-G-C is Benign according to our data. Variant chr8-89924970-G-C is described in ClinVar as [Benign]. Clinvar id is 713505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1810/152322) while in subpopulation AFR AF= 0.0415 (1725/41568). AF 95% confidence interval is 0.0399. There are 36 homozygotes in gnomad4. There are 877 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OSGIN2	NM_001126111.3 linkuse as main transcript	c.1088G>C	p.Cys363Ser	missense_variant	6/6	ENST00000451899.7	NP_001119583.1
OSGIN2	NM_004337.2 linkuse as main transcript	c.956G>C	p.Cys319Ser	missense_variant	6/6		NP_004328.1
OSGIN2	XM_011517287.4 linkuse as main transcript	c.956G>C	p.Cys319Ser	missense_variant	6/6		XP_011515589.1
OSGIN2	XM_011517288.4 linkuse as main transcript	c.557G>C	p.Cys186Ser	missense_variant	3/3		XP_011515590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSGIN2	ENST00000451899.7 linkuse as main transcript	c.1088G>C	p.Cys363Ser	missense_variant	6/6	1	NM_001126111.3	ENSP00000396445		Q9Y236-2
OSGIN2	ENST00000297438.6 linkuse as main transcript	c.956G>C	p.Cys319Ser	missense_variant	6/6	1		ENSP00000297438	P1	Q9Y236-1
OSGIN2	ENST00000647849.1 linkuse as main transcript	c.956G>C	p.Cys319Ser	missense_variant	6/6			ENSP00000497119	P1	Q9Y236-1
NBN	ENST00000697292.1 linkuse as main transcript	c.*410C>G		3_prime_UTR_variant	17/17			ENSP00000513229	P1

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1800

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00299

AC:

749

AN:

250632

Hom.:

AF XY:

0.00206

AC XY:

279

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00114

AC:

1667

AN:

1461564

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

693

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0416

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.0119

AC:

1810

AN:

152322

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

877

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0415

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.0135

ESP6500AA

AF:

0.0402

AC:

177

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00361

AC:

438

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

T;T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

.;T;T

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.4

.;N;N

REVEL

Benign

0.22

Sift

Benign

0.16

.;T;T

Sift4G

Benign

0.39

.;T;T

Polyphen

0.97

D;D;D

Vest4

0.66, 0.67

MutPred

0.15

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;

MVP

0.19

MPC

0.67

ClinPred

0.039

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.68

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over