17-27765605-A-C

Variant names:

• chr17-27765605-A-C
• rs1060822
• NM_000625.4:c.2358T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000625.4(NOS2):​c.2358T>G​(p.Gly786Gly) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. G786G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NOS2 NM_000625.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• Publications: 19 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.751 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	NM_000625.4	MANE Select	c.2358T>G	p.Gly786Gly	synonymous	Exon 20 of 27	NP_000616.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS2	ENST00000313735.11	TSL:1 MANE Select	c.2358T>G	p.Gly786Gly	synonymous	Exon 20 of 27	ENSP00000327251.6
	NOS2	ENST00000646938.1		c.2355T>G	p.Gly785Gly	synonymous	Exon 19 of 26	ENSP00000494870.1
	NOS2	ENST00000697338.1		n.*1804T>G		non_coding_transcript_exon	Exon 18 of 25	ENSP00000513260.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		0.75

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: rs1060822; hg19: chr17-26092631;