rs2066843

Variant names:

• chr16-50711288-C-T
• rs2066843
• NM_001370466.1:c.1296C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-50711288-C-T
• chr16-50711288-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001370466.1(NOD2):​c.1296C>T​(p.Arg432Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,584 control chromosomes in the GnomAD database, including 49,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3255 hom., cov: 33)
  • Exomes 𝑓: 0.24 (46409 hom.)
• Consequence: NOD2 NM_001370466.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.0500
• Publications: 70 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: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina
• inflammatory bowel disease 1

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 16-50711288-C-T is Benign according to our data. Variant chr16-50711288-C-T is described in ClinVar as Benign. ClinVar VariationId is 319445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	NM_001370466.1	MANE Select	c.1296C>T	p.Arg432Arg	synonymous	Exon 4 of 12	NP_001357395.1	Q9HC29-2
	NOD2	NM_022162.3		c.1377C>T	p.Arg459Arg	synonymous	Exon 4 of 12	NP_071445.1	Q9HC29-1
	NOD2	NM_001293557.2		c.1296C>T	p.Arg432Arg	synonymous	Exon 3 of 11	NP_001280486.1	Q9HC29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	ENST00000647318.2	MANE Select	c.1296C>T	p.Arg432Arg	synonymous	Exon 4 of 12	ENSP00000495993.1	Q9HC29-2
	NOD2	ENST00000300589.6	TSL:1	c.1377C>T	p.Arg459Arg	synonymous	Exon 4 of 12	ENSP00000300589.2	Q9HC29-1
	NOD2	ENST00000951248.1		c.1296C>T	p.Arg432Arg	synonymous	Exon 4 of 12	ENSP00000621307.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27624 AN: 152088 Hom.: 3253 Cov.: 33

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00868

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.220

GnomAD2 exomes AF: 0.190 AC: 47482 AN: 250080 AF XY: 0.197

Gnomad AFR exome AF: 0.0584

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.00561

Gnomad FIN exome AF: 0.161

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.240 AC: 351405 AN: 1461378 Hom.: 46409 Cov.: 47 AF XY: 0.239 AC XY: 174102 AN XY: 727016

African (AFR) AF: 0.0573 AC: 1917 AN: 33478

American (AMR) AF: 0.130 AC: 5803 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6267 AN: 26136

East Asian (EAS) AF: 0.00338 AC: 134 AN: 39700

South Asian (SAS) AF: 0.147 AC: 12696 AN: 86258

European-Finnish (FIN) AF: 0.162 AC: 8591 AN: 52920

Middle Eastern (MID) AF: 0.254 AC: 1467 AN: 5768

European-Non Finnish (NFE) AF: 0.271 AC: 301368 AN: 1112000

Other (OTH) AF: 0.218 AC: 13162 AN: 60394

GnomAD4 genome AF: 0.182 AC: 27631 AN: 152206 Hom.: 3255 Cov.: 33 AF XY: 0.177 AC XY: 13150 AN XY: 74416

African (AFR) AF: 0.0624 AC: 2593 AN: 41548

American (AMR) AF: 0.180 AC: 2758 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3468

East Asian (EAS) AF: 0.00870 AC: 45 AN: 5174

South Asian (SAS) AF: 0.128 AC: 617 AN: 4830

European-Finnish (FIN) AF: 0.159 AC: 1683 AN: 10598

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18285 AN: 67974

Other (OTH) AF: 0.220 AC: 465 AN: 2110

Alfa AF: 0.243 Hom.: 14090

Bravo AF: 0.177

Asia WGS AF: 0.0730 AC: 260 AN: 3478

EpiCase AF: 0.280

EpiControl AF: 0.273

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Blau syndrome (1)
-	-	1	Inflammatory bowel disease 1 (1)
-	-	1	Regional enteritis;C5201146:Blau syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.7
DANN	Benign	0.37
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

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: rs2066843; hg19: chr16-50745199; COSMIC: COSV56048410; COSMIC: COSV56048410;