rs2297511

Variant names:

• chr17-27764201-C-G
• rs2297511
• NM_000625.4:c.2429-57G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-27764201-C-G
• chr17-27764201-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000625.4(NOS2):​c.2429-57G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NOS2 NM_000625.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 3 publications found

Genes affected

NOS2 (HGNC:7873): (nitric oxide synthase 2) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

NOS2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOS2	NM_000625.4	c.2429-57G>C		intron_variant	Intron 20 of 26	ENST00000313735.11	NP_000616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOS2	ENST00000313735.11	c.2429-57G>C		intron_variant	Intron 20 of 26	1	NM_000625.4	ENSP00000327251.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 844092 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 419902

African (AFR) AF: 0.00 AC: 0 AN: 13882

American (AMR) AF: 0.00 AC: 0 AN: 15994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14866

East Asian (EAS) AF: 0.00 AC: 0 AN: 26468

South Asian (SAS) AF: 0.00 AC: 0 AN: 44142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 644976

Other (OTH) AF: 0.00 AC: 0 AN: 36480

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.35
PhyloP100		-0.44

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: rs2297511; hg19: chr17-26091227;