chr16-50711672-T-G

Position:

chr16-50711672-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370466.1(NOD2):c.1680T>G(p.Arg560=) 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:8O:1

Conservation

PhyloP100: -1.55

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 319450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-50711672-T-G is described in Lovd as [Benign].

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/exons	MANE	UniProt
NOD2	NM_001370466.1 linkuse as main transcript	c.1680T>G	p.Arg560=	synonymous_variant	4/12	ENST00000647318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD2	ENST00000647318.2 linkuse as main transcript	c.1680T>G	p.Arg560=	synonymous_variant	4/12		NM_001370466.1	P1	Q9HC29-2
NOD2	ENST00000300589.6 linkuse as main transcript	c.1761T>G	p.Arg587=	synonymous_variant	4/12	1			Q9HC29-1
NOD2	ENST00000641284.2 linkuse as main transcript	c.1680T>G	p.Arg560=	synonymous_variant, NMD_transcript_variant	4/6
NOD2	ENST00000646677.2 linkuse as main transcript	c.1680T>G	p.Arg560=	synonymous_variant, NMD_transcript_variant	4/13

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

GnomAD3 exomes

AF:

0.329

AC:

82175

AN:

249426

Hom.:

15033

AF XY:

0.331

AC XY:

44695

AN XY:

134878

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 SAS exome

AF:

0.229

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

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.283

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.400

Gnomad4 NFE exome

AF:

0.390

Gnomad4 OTH exome

AF:

0.357

GnomAD4 genome

AF:

0.320

AC:

48665

AN:

152168

Hom.:

8582

Cov.:

AF XY:

0.315

AC XY:

23452

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.318

Gnomad4 ASJ

AF:

0.536

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.329

Alfa

AF:

0.370

Hom.:

6552

Bravo

AF:

0.312

Asia WGS

AF:

0.163

AC:

564

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	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. -

Regional enteritis;C5201146:Blau syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Inflammatory bowel disease 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.28

DANN

Benign

0.42

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