rs17221417

Variant names:

• chr16-50705671-C-G
• rs17221417
• NM_001370466.1:c.460-2184C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370466.1(NOD2):​c.460-2184C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,168 control chromosomes in the GnomAD database, including 3,854 homozygotes. 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: 𝑓 0.20 (3854 hom., cov: 32)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 57 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 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.460-2184C>G		intron	N/A	NP_001357395.1	Q9HC29-2
	NOD2	NM_022162.3		c.541-2184C>G		intron	N/A	NP_071445.1	Q9HC29-1
	NOD2	NM_001293557.2		c.460-2184C>G		intron	N/A	NP_001280486.1	Q9HC29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOD2	ENST00000647318.2	MANE Select	c.460-2184C>G		intron	N/A	ENSP00000495993.1	Q9HC29-2
	NOD2	ENST00000300589.6	TSL:1	c.541-2184C>G		intron	N/A	ENSP00000300589.2	Q9HC29-1
	NOD2	ENST00000527070.5	TSL:1	c.460-2184C>G		intron	N/A	ENSP00000435149.2	E9PLF7

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30028 AN: 152050 Hom.: 3854 Cov.: 32

Gnomad AFR AF: 0.0651

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.00886

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.231

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.197 AC: 30031 AN: 152168 Hom.: 3854 Cov.: 32 AF XY: 0.193 AC XY: 14327 AN XY: 74392

African (AFR) AF: 0.0649 AC: 2697 AN: 41542

American (AMR) AF: 0.195 AC: 2988 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3466

East Asian (EAS) AF: 0.00888 AC: 46 AN: 5182

South Asian (SAS) AF: 0.134 AC: 645 AN: 4814

European-Finnish (FIN) AF: 0.197 AC: 2083 AN: 10558

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19855 AN: 67996

Other (OTH) AF: 0.232 AC: 489 AN: 2108

Alfa AF: 0.231 Hom.: 599

Bravo AF: 0.191

Asia WGS AF: 0.0740 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.43
PhyloP100		-0.083
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: rs17221417; hg19: chr16-50739582; COSMIC: COSV56052932;