NM_001126111.3:c.1024C>A

Variant names:

• chr8-89924906-C-A
• rs533674331
• NM_001126111.3:c.1024C>A

Variant summary

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

The NM_001126111.3(OSGIN2):​c.1024C>A​(p.Arg342Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: OSGIN2 NM_001126111.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33

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=0.06632072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGIN2	NM_001126111.3	c.1024C>A	p.Arg342Ser	missense_variant	Exon 6 of 6	ENST00000451899.7	NP_001119583.1
OSGIN2	NM_004337.2	c.892C>A	p.Arg298Ser	missense_variant	Exon 6 of 6		NP_004328.1
OSGIN2	XM_011517287.4	c.892C>A	p.Arg298Ser	missense_variant	Exon 6 of 6		XP_011515589.1
OSGIN2	XM_011517288.4	c.493C>A	p.Arg165Ser	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.1024C>A	p.Arg342Ser	missense_variant	Exon 6 of 6	1	NM_001126111.3	ENSP00000396445.2
OSGIN2	ENST00000297438.6	c.892C>A	p.Arg298Ser	missense_variant	Exon 6 of 6	1		ENSP00000297438.2
OSGIN2	ENST00000647849.1	c.892C>A	p.Arg298Ser	missense_variant	Exon 6 of 6			ENSP00000497119.1
NBN	ENST00000697292	c.*474G>T		3_prime_UTR_variant	Exon 17 of 17			ENSP00000513229.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250894 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135554

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461862 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727230

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: 0.00000989

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	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.87
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.72	.;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N;N;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.14	.;N;N
REVEL	Benign	0.026
Sift	Benign	0.77	.;T;T
Sift4G	Benign	0.76	.;T;T
Polyphen		0.0010	B;B;B
Vest4		0.085, 0.066
MutPred		0.39		Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);.;
MVP		0.12
MPC		0.39
ClinPred		0.073	T
GERP RS		2.7
Varity_R		0.095
gMVP		0.33

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: rs533674331; hg19: chr8-90937134;