rs749844272

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001126111.3(OSGIN2):c.662G>A(p.Arg221His) variant causes a missense change. The variant allele was found at a frequency of 0.0000595 in 1,612,318 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

OSGIN2
NM_001126111.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

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:

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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=0.165725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN2	NM_001126111.3 link	c.662G>A	p.Arg221His	missense_variant	Exon 6 of 6	ENST00000451899.7	NP_001119583.1	Q9Y236-2
OSGIN2	NM_004337.2 link	c.530G>A	p.Arg177His	missense_variant	Exon 6 of 6		NP_004328.1	Q9Y236-1A0A024R9D5
OSGIN2	XM_011517287.4 link	c.530G>A	p.Arg177His	missense_variant	Exon 6 of 6		XP_011515589.1	Q9Y236-1A0A024R9D5
OSGIN2	XM_011517288.4 link	c.131G>A	p.Arg44His	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.662G>A	p.Arg221His	missense_variant	Exon 6 of 6	1	NM_001126111.3	ENSP00000396445.2	Q9Y236-2
OSGIN2	ENST00000297438.6 link	c.530G>A	p.Arg177His	missense_variant	Exon 6 of 6	1		ENSP00000297438.2	Q9Y236-1
OSGIN2	ENST00000647849.1 link	c.530G>A	p.Arg177His	missense_variant	Exon 6 of 6			ENSP00000497119.1	Q9Y236-1
NBN	ENST00000697292 link	c.*836C>T		3_prime_UTR_variant	Exon 17 of 17			ENSP00000513229.1	O60934

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000562

AC:

AN:

248966

Hom.:

AF XY:

0.0000668

AC XY:

AN XY:

134806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000878

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000623

AC:

AN:

1460302

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

726408

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000666

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.662G>A (p.R221H) alteration is located in exon 6 (coding exon 6) of the OSGIN2 gene. This alteration results from a G to A substitution at nucleotide position 662, causing the arginine (R) at amino acid position 221 to be replaced by a histidine (H). 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

0.067

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.66

.;N;N

REVEL

Benign

0.050

Sift

Benign

0.48

.;T;T

Sift4G

Benign

0.20

.;T;T

Polyphen

0.047

B;B;B

Vest4

0.061, 0.068

MutPred

0.42

Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);.;

MVP

0.16

MPC

0.43

ClinPred

0.057

GERP RS

5.2

Varity_R

0.18

gMVP

0.40

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