chr16-50719952-G-A

Variant names:

• chr16-50719952-G-A
• rs1417676866
• NM_001370466.1:c.2577G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001370466.1(NOD2):​c.2577G>A​(p.Ala859Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: NOD2 NM_001370466.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.50
• Publications: 1 publications found

Genes affected

NOD2 (HGNC:5331): (nucleotide binding oligomerization domain containing 2) This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

NOD2 Gene-Disease associations (from GenCC):

• Blau syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Genomics England PanelApp, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• inflammatory bowel disease 1

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

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.056).
• BP6: Variant 16-50719952-G-A is Benign according to our data. Variant chr16-50719952-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 531598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.49 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 10 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370466.1. 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
	NOD2	NM_001370466.1	MANE Select	c.2577G>A	p.Ala859Ala	synonymous	Exon 7 of 12	NP_001357395.1
	NOD2	NM_022162.3		c.2658G>A	p.Ala886Ala	synonymous	Exon 7 of 12	NP_071445.1
	NOD2	NM_001293557.2		c.2577G>A	p.Ala859Ala	synonymous	Exon 6 of 11	NP_001280486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	ENST00000647318.2	MANE Select	c.2577G>A	p.Ala859Ala	synonymous	Exon 7 of 12	ENSP00000495993.1
	NOD2	ENST00000300589.6	TSL:1	c.2658G>A	p.Ala886Ala	synonymous	Exon 7 of 12	ENSP00000300589.2
	NOD2	ENST00000534057.1	TSL:1	c.291G>A	p.Ala97Ala	synonymous	Exon 3 of 5	ENSP00000437246.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251464 AF XY: 0.00000736

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Regional enteritis;C5201146:Blau syndrome Benign:1

Oct 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.052
DANN	Benign	0.35
PhyloP100		-4.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1417676866; hg19: chr16-50753863;