rs529610109

Variant names:

• chr8-89924709-A-C
• rs529610109
• NM_001126111.3:c.827A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-89924709-A-C
• chr8-89924709-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001126111.3(OSGIN2):​c.827A>C​(p.Lys276Thr) 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 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K276R) has been classified as Uncertain significance.

• 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: 2.84
• Publications: 0 publications found

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]

NBN Gene-Disease associations (from GenCC):

• Nijmegen breakage syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P, Orphanet, ClinGen
• rhabdomyosarcoma

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• idiopathic aplastic anemia

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.118989915).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126111.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGIN2	NM_001126111.3	MANE Select	c.827A>C	p.Lys276Thr	missense	Exon 6 of 6	NP_001119583.1	Q9Y236-2
	OSGIN2	NM_004337.2		c.695A>C	p.Lys232Thr	missense	Exon 6 of 6	NP_004328.1	Q9Y236-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGIN2	ENST00000451899.7	TSL:1 MANE Select	c.827A>C	p.Lys276Thr	missense	Exon 6 of 6	ENSP00000396445.2	Q9Y236-2
	OSGIN2	ENST00000297438.6	TSL:1	c.695A>C	p.Lys232Thr	missense	Exon 6 of 6	ENSP00000297438.2	Q9Y236-1
	OSGIN2	ENST00000869563.1		c.785A>C	p.Lys262Thr	missense	Exon 6 of 6	ENSP00000539622.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250786 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 6.84e-7 AC: 1 AN: 1461766 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.12
Sift	Benign	0.36	T
Sift4G	Benign	0.41	T
Polyphen		0.16	B
Vest4		0.38
MutPred		0.36		Gain of sheet (P = 0.0043)
MVP		0.31
MPC		0.42
ClinPred		0.18	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.065
gMVP		0.47
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs529610109; hg19: chr8-90936937;