8-89924970-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.78

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSGIN2	NM_001126111.3	c.1088G>C	p.Cys363Ser	missense_variant	6/6	ENST00000451899.7
OSGIN2	NM_004337.2	c.956G>C	p.Cys319Ser	missense_variant	6/6
OSGIN2	XM_011517287.4	c.956G>C	p.Cys319Ser	missense_variant	6/6
OSGIN2	XM_011517288.4	c.557G>C	p.Cys186Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGIN2	ENST00000451899.7	c.1088G>C	p.Cys363Ser	missense_variant	6/6	1	NM_001126111.3
OSGIN2	ENST00000297438.6	c.956G>C	p.Cys319Ser	missense_variant	6/6	1		P1
OSGIN2	ENST00000647849.1	c.956G>C	p.Cys319Ser	missense_variant	6/6			P1
NBN	ENST00000697292.1	c.*410C>G		3_prime_UTR_variant	17/17			P1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1800 AN: 152204 Hom.: 36 Cov.: 32

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.: 16 AF XY: 0.00206 AC XY: 279 AN XY: 135418

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.: 46 Cov.: 32 AF XY: 0.000953 AC XY: 693 AN XY: 727104

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.: 36 Cov.: 32 AF XY: 0.0118 AC XY: 877 AN XY: 74488

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.: 4

Bravo AF: 0.0135

ESP6500AA AF: 0.0402 AC: 177

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00361 AC: 438

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.062	T;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
MetaRNN	Benign	0.0085	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.73	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	T
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

Other links and lift over

dbSNP: rs35599414; hg19: chr8-90937198;