chr8-89924933-G-T

Position:

• chr8-89924933-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001126111.3(OSGIN2):​c.1051G>T​(p.Val351Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSGIN2 NM_001126111.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSGIN2	NM_001126111.3	c.1051G>T	p.Val351Leu	missense_variant	6/6	ENST00000451899.7	NP_001119583.1
OSGIN2	NM_004337.2	c.919G>T	p.Val307Leu	missense_variant	6/6		NP_004328.1
OSGIN2	XM_011517287.4	c.919G>T	p.Val307Leu	missense_variant	6/6		XP_011515589.1
OSGIN2	XM_011517288.4	c.520G>T	p.Val174Leu	missense_variant	3/3		XP_011515590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSGIN2	ENST00000451899.7	c.1051G>T	p.Val351Leu	missense_variant	6/6	1	NM_001126111.3	ENSP00000396445
OSGIN2	ENST00000297438.6	c.919G>T	p.Val307Leu	missense_variant	6/6	1		ENSP00000297438	P1
OSGIN2	ENST00000647849.1	c.919G>T	p.Val307Leu	missense_variant	6/6			ENSP00000497119	P1
NBN	ENST00000697292.1	c.*447C>A		3_prime_UTR_variant	17/17			ENSP00000513229	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.1051G>T (p.V351L) alteration is located in exon 6 (coding exon 6) of the OSGIN2 gene. This alteration results from a G to T substitution at nucleotide position 1051, causing the valine (V) at amino acid position 351 to be replaced by a leucine (L). 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	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;T;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.0	M;M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.3	.;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.020	.;D;D
Sift4G	Uncertain	0.011	.;D;D
Polyphen		0.96	D;D;D
Vest4		0.53, 0.53
MutPred		0.60		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;
MVP		0.46
MPC		0.69
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.20
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-90937161;