rs150510939

Variant names:

• chr8-89925128-T-A
• NM_001126111.3:c.1246T>A

Your query was ambiguous. Multiple possible variants found:

• chr8-89925128-T-A
• chr8-89925128-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001126111.3(OSGIN2):​c.1246T>A​(p.Leu416Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L416L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OSGIN2 NM_001126111.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054963887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN2	NM_001126111.3	c.1246T>A	p.Leu416Ile	missense_variant	Exon 6 of 6	ENST00000451899.7	NP_001119583.1
OSGIN2	NM_004337.2	c.1114T>A	p.Leu372Ile	missense_variant	Exon 6 of 6		NP_004328.1
OSGIN2	XM_011517287.4	c.1114T>A	p.Leu372Ile	missense_variant	Exon 6 of 6		XP_011515589.1
OSGIN2	XM_011517288.4	c.715T>A	p.Leu239Ile	missense_variant	Exon 3 of 3		XP_011515590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGIN2	ENST00000451899.7	c.1246T>A	p.Leu416Ile	missense_variant	Exon 6 of 6	1	NM_001126111.3	ENSP00000396445.2
OSGIN2	ENST00000297438.6	c.1114T>A	p.Leu372Ile	missense_variant	Exon 6 of 6	1		ENSP00000297438.2
OSGIN2	ENST00000647849.1	c.1114T>A	p.Leu372Ile	missense_variant	Exon 6 of 6			ENSP00000497119.1
NBN	ENST00000697292	c.*252A>T		3_prime_UTR_variant	Exon 17 of 17			ENSP00000513229.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.041	T;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.28	.;N;N
REVEL	Benign	0.024
Sift	Benign	0.060	.;T;T
Sift4G	Benign	0.26	.;T;T
Polyphen		0.018	B;B;B
Vest4		0.12, 0.14
MVP		0.15
MPC		0.38
ClinPred		0.037	T
GERP RS		0.050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.16

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: chr8-90937356;