chr16-50711672-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370466.1(NOD2):c.1680T>G(p.Arg560Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,612,716 control chromosomes in the GnomAD database, including 111,633 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8582 hom., cov: 33)

Exomes 𝑓: 0.37 ( 103051 hom. )

Consequence

NOD2
NM_001370466.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -1.55

Publications

53 publications found

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 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)

NOD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

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

BP6

Variant 16-50711672-T-G is Benign according to our data. Variant chr16-50711672-T-G is described in ClinVar as Benign. ClinVar VariationId is 319450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1 link	c.1680T>G	p.Arg560Arg	synonymous_variant	Exon 4 of 12	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NOD2	ENST00000647318.2 link	c.1680T>G	p.Arg560Arg	synonymous_variant	Exon 4 of 12		NM_001370466.1	ENSP00000495993.1	Q9HC29-2
NOD2	ENST00000300589.6 link	c.1761T>G	p.Arg587Arg	synonymous_variant	Exon 4 of 12	1		ENSP00000300589.2	Q9HC29-1
NOD2	ENST00000641284.2 link	n.1680T>G		non_coding_transcript_exon_variant	Exon 4 of 6			ENSP00000493088.1	A0A286YF65
NOD2	ENST00000646677.2 link	n.1680T>G		non_coding_transcript_exon_variant	Exon 4 of 13			ENSP00000496533.1	A0A286YF65

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48660

AN:

152050

Hom.:

8585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.334

GnomAD2 exomes

AF:

0.329

AC:

82175

AN:

249426

AF XY:

0.331

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.397

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.367

AC:

536574

AN:

1460548

Hom.:

103051

Cov.:

AF XY:

0.365

AC XY:

264896

AN XY:

726538

show subpopulations

African (AFR)

AF:

0.190

AC:

6368

AN:

33476

American (AMR)

AF:

0.283

AC:

12619

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

14064

AN:

26130

East Asian (EAS)

AF:

0.126

AC:

4983

AN:

39654

South Asian (SAS)

AF:

0.232

AC:

20022

AN:

86206

European-Finnish (FIN)

AF:

0.400

AC:

21109

AN:

52772

Middle Eastern (MID)

AF:

0.385

AC:

2217

AN:

5764

European-Non Finnish (NFE)

AF:

0.390

AC:

433666

AN:

1111560

Other (OTH)

AF:

0.357

AC:

21526

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

22095

44191

66286

88382

110477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13242

26484

39726

52968

66210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.320

AC:

48665

AN:

152168

Hom.:

8582

Cov.:

AF XY:

0.315

AC XY:

23452

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.194

AC:

8061

AN:

41518

American (AMR)

AF:

0.318

AC:

4862

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

1859

AN:

3470

East Asian (EAS)

AF:

0.104

AC:

537

AN:

5176

South Asian (SAS)

AF:

0.205

AC:

991

AN:

4826

European-Finnish (FIN)

AF:

0.399

AC:

4216

AN:

10576

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.397

AC:

26955

AN:

67978

Other (OTH)

AF:

0.329

AC:

697

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1677

3354

5032

6709

8386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

478

956

1434

1912

2390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.368

Hom.:

7313

Bravo

AF:

0.312

Asia WGS

AF:

0.163

AC:

564

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -

not provided

Benign:2Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Nov 26, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Regional enteritis;C5201146:Blau syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inflammatory bowel disease 1

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.28

(source)

DANN

Benign

0.42

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over