rs2076756

Variant names:

• chr16-50722970-A-G
• rs2076756
• NM_001370466.1:c.2717+265A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370466.1(NOD2):​c.2717+265A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,902 control chromosomes in the GnomAD database, including 2,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.17 (2890 hom., cov: 31)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.293
• Publications: 99 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-50722970-A-G is Benign according to our data. Variant chr16-50722970-A-G is described in ClinVar as Benign. ClinVar VariationId is 1261773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 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.2717+265A>G		intron	N/A	NP_001357395.1	Q9HC29-2
	NOD2	NM_022162.3		c.2798+265A>G		intron	N/A	NP_071445.1	Q9HC29-1
	NOD2	NM_001293557.2		c.2717+265A>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.2717+265A>G		intron	N/A	ENSP00000495993.1	Q9HC29-2
	NOD2	ENST00000300589.6	TSL:1	c.2798+265A>G		intron	N/A	ENSP00000300589.2	Q9HC29-1
	NOD2	ENST00000534057.1	TSL:1	c.431+265A>G		intron	N/A	ENSP00000437246.1	H0YF53

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26009 AN: 151784 Hom.: 2889 Cov.: 31

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.00813

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.171 AC: 26017 AN: 151902 Hom.: 2890 Cov.: 31 AF XY: 0.166 AC XY: 12342 AN XY: 74258

African (AFR) AF: 0.0601 AC: 2489 AN: 41430

American (AMR) AF: 0.159 AC: 2427 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 813 AN: 3462

East Asian (EAS) AF: 0.00815 AC: 42 AN: 5152

South Asian (SAS) AF: 0.128 AC: 616 AN: 4800

European-Finnish (FIN) AF: 0.153 AC: 1611 AN: 10556

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17247 AN: 67920

Other (OTH) AF: 0.204 AC: 429 AN: 2108

Alfa AF: 0.227 Hom.: 18854

Bravo AF: 0.165

Asia WGS AF: 0.0730 AC: 260 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.29
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: rs2076756; hg19: chr16-50756881;