8-89902800-G-C

Position:

• chr8-89902800-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001126111.3(OSGIN2):​c.7G>C​(p.Val3Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000251 in 1,194,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000025 (1 hom.)
• Consequence: OSGIN2 NM_001126111.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3174292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSGIN2	NM_001126111.3	c.7G>C	p.Val3Leu	missense_variant	1/6	ENST00000451899.7	NP_001119583.1
OSGIN2	NM_004337.2	c.-89+675G>C		intron_variant			NP_004328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSGIN2	ENST00000451899.7	c.7G>C	p.Val3Leu	missense_variant	1/6	1	NM_001126111.3	ENSP00000396445
OSGIN2	ENST00000297438.6	c.-89+675G>C		intron_variant		1		ENSP00000297438	P1
OSGIN2	ENST00000520659.1	c.7G>C	p.Val3Leu	missense_variant	1/5	2		ENSP00000431029
OSGIN2	ENST00000647849.1	c.-89+889G>C		intron_variant				ENSP00000497119	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000251 AC: 3 AN: 1194634 Hom.: 1 Cov.: 29 AF XY: 0.00000518 AC XY: 3 AN XY: 579230

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: 0.00000312

Gnomad4 OTH exome AF: 0.00

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

Dec 19, 2022

The c.7G>C (p.V3L) alteration is located in exon 1 (coding exon 1) of the OSGIN2 gene. This alteration results from a G to C substitution at nucleotide position 7, causing the valine (V) at amino acid position 3 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
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	26
DANN	Uncertain	0.99
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.74	T;T
M_CAP	Pathogenic	0.47	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.79	T
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.021	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.41
MutPred		0.24		Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);
MVP		0.32
MPC		1.1
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.29

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: chr8-90915028;