rs779252565

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001126111.3(OSGIN2):c.1018A>C(p.Lys340Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,054 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 1 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.071058184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN2	NM_001126111.3 link	c.1018A>C	p.Lys340Gln	missense_variant	Exon 6 of 6	ENST00000451899.7	NP_001119583.1	Q9Y236-2
OSGIN2	NM_004337.2 link	c.886A>C	p.Lys296Gln	missense_variant	Exon 6 of 6		NP_004328.1	Q9Y236-1A0A024R9D5
OSGIN2	XM_011517287.4 link	c.886A>C	p.Lys296Gln	missense_variant	Exon 6 of 6		XP_011515589.1	Q9Y236-1A0A024R9D5
OSGIN2	XM_011517288.4 link	c.487A>C	p.Lys163Gln	missense_variant	Exon 3 of 3		XP_011515590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OSGIN2	ENST00000451899.7 link	c.1018A>C	p.Lys340Gln	missense_variant	Exon 6 of 6	1	NM_001126111.3	ENSP00000396445.2	Q9Y236-2
OSGIN2	ENST00000297438.6 link	c.886A>C	p.Lys296Gln	missense_variant	Exon 6 of 6	1		ENSP00000297438.2	Q9Y236-1
OSGIN2	ENST00000647849.1 link	c.886A>C	p.Lys296Gln	missense_variant	Exon 6 of 6			ENSP00000497119.1	Q9Y236-1
NBN	ENST00000697292 link	c.*480T>G		3_prime_UTR_variant	Exon 17 of 17			ENSP00000513229.1	O60934

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

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:

0.0000239

AC:

AN:

250982

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1018A>C (p.K340Q) 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 1018, causing the lysine (K) at amino acid position 340 to be replaced by a glutamine (Q). 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

0.080

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.023

T;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.014

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.62

.;N;N

REVEL

Benign

0.035

Sift

Benign

0.37

.;T;T

Sift4G

Benign

0.41

.;T;T

Polyphen

0.015

B;B;B

Vest4

0.099, 0.11

MutPred

0.35

Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);.;

MVP

0.25

MPC

0.37

ClinPred

0.10

GERP RS

4.3

Varity_R

0.18

gMVP

0.54

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