dbSNP rs2067085: NOD2:p.Ser151Ser (chr16-50699948-C-G) – ACMG Classification: Benign (-21 pts)

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.453C>G(p.Ser151Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,604,806 control chromosomes in the GnomAD database, including 115,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10039 hom., cov: 31)

Exomes 𝑓: 0.37 ( 105338 hom. )

Consequence

NOD2
NM_001370466.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.355

Publications

40 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: 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)

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=-0.53).

BP6

Variant 16-50699948-C-G is Benign according to our data. Variant chr16-50699948-C-G is described in ClinVar as Benign. ClinVar VariationId is 319429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.355 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOD2	NM_001370466.1	MANE Select	c.453C>G	p.Ser151Ser	synonymous	Exon 2 of 12	NP_001357395.1	Q9HC29-2
NOD2	NM_022162.3		c.534C>G	p.Ser178Ser	synonymous	Exon 2 of 12	NP_071445.1	Q9HC29-1
NOD2	NM_001293557.2		c.453C>G	p.Ser151Ser	synonymous	Exon 1 of 11	NP_001280486.1	Q9HC29-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOD2	ENST00000647318.2	MANE Select	c.453C>G	p.Ser151Ser	synonymous	Exon 2 of 12	ENSP00000495993.1	Q9HC29-2
NOD2	ENST00000300589.6	TSL:1	c.534C>G	p.Ser178Ser	synonymous	Exon 2 of 12	ENSP00000300589.2	Q9HC29-1
NOD2	ENST00000527070.5	TSL:1	c.453C>G	p.Ser151Ser	synonymous	Exon 2 of 4	ENSP00000435149.2	E9PLF7

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53564

AN:

151888

Hom.:

10040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.0517

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.331

AC:

80774

AN:

243838

AF XY:

0.334

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.530

Gnomad EAS exome

AF:

0.0592

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.372

AC:

540163

AN:

1452798

Hom.:

105338

Cov.:

AF XY:

0.369

AC XY:

266990

AN XY:

722980

show subpopulations

African (AFR)

AF:

0.293

AC:

9807

AN:

33468

American (AMR)

AF:

0.259

AC:

11572

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.538

AC:

14065

AN:

26132

East Asian (EAS)

AF:

0.0566

AC:

2246

AN:

39656

South Asian (SAS)

AF:

0.242

AC:

20896

AN:

86234

European-Finnish (FIN)

AF:

0.429

AC:

19438

AN:

45326

Middle Eastern (MID)

AF:

0.390

AC:

2245

AN:

5756

European-Non Finnish (NFE)

AF:

0.394

AC:

437963

AN:

1111232

Other (OTH)

AF:

0.364

AC:

21931

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16695

33389

50084

66778

83473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13342

26684

40026

53368

66710

<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:

0.352

AC:

53566

AN:

152008

Hom.:

10039

Cov.:

AF XY:

0.349

AC XY:

25966

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.292

AC:

12120

AN:

41436

American (AMR)

AF:

0.346

AC:

5284

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

1863

AN:

3470

East Asian (EAS)

AF:

0.0516

AC:

267

AN:

5172

South Asian (SAS)

AF:

0.215

AC:

1034

AN:

4818

European-Finnish (FIN)

AF:

0.434

AC:

4588

AN:

10564

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27177

AN:

67948

Other (OTH)

AF:

0.352

AC:

744

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1722

3444

5167

6889

8611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.321

Hom.:

1513

Bravo

AF:

0.342

Asia WGS

AF:

0.141

AC:

491

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.405

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Blau syndrome (1)

Inflammatory bowel disease 1 (1)

Regional enteritis;C5201146:Blau syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.6

(source)

DANN

Benign

0.58

PhyloP100

-0.35

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over