rs2076752

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000300589.6(NOD2):c.-59G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,429,068 control chromosomes in the GnomAD database, including 52,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4118 hom., cov: 33)

Exomes 𝑓: 0.26 ( 47959 hom. )

Consequence

NOD2
ENST00000300589.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.998

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-50697185-G-A is Benign according to our data. Variant chr16-50697185-G-A is described in ClinVar as [Benign]. Clinvar id is 319419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD2	NM_001370466.1 linkuse as main transcript	c.-8-2303G>A		intron_variant		ENST00000647318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD2	ENST00000647318.2 linkuse as main transcript	c.-8-2303G>A		intron_variant			NM_001370466.1	P1	Q9HC29-2

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33059

AN:

152074

Hom.:

4117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.00943

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.263

AC:

335224

AN:

1276876

Hom.:

47959

Cov.:

AF XY:

0.261

AC XY:

166090

AN XY:

635932

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.149

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.00437

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.291

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.217

AC:

33078

AN:

152192

Hom.:

4118

Cov.:

AF XY:

0.212

AC XY:

15741

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.243

Gnomad4 EAS

AF:

0.00945

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.262

Hom.:

3701

Bravo

AF:

0.214

Asia WGS

AF:

0.0870

AC:

310

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 30% of patients studied by a panel of primary immunodeficiencies. Number of patients: 29. Only high quality variants are reported. -

Inflammatory bowel disease 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Blau syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

Cadd

Benign

0.48

Dann

Benign

0.37

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over