rs2111235

Variant names:

• chr16-50700058-A-G
• rs2111235
• NM_001370466.1:c.459+104A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-50700058-A-G
• chr16-50700058-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001370466.1(NOD2):​c.459+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,093,490 control chromosomes in the GnomAD database, including 236,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (32992 hom., cov: 32)
  • Exomes 𝑓: 0.65 (203089 hom.)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-50700058-A-G is Benign according to our data. Variant chr16-50700058-A-G is described in ClinVar as [Benign]. Clinvar id is 2688412.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.459+104A>G		intron_variant	Intron 2 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.459+104A>G		intron_variant	Intron 2 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98978 AN: 151980 Hom.: 32987 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.662

GnomAD4 exome AF: 0.647 AC: 609201 AN: 941392 Hom.: 203089 AF XY: 0.643 AC XY: 308777 AN XY: 480562

Gnomad4 AFR exome AF: 0.665

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.799

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.638

GnomAD4 genome AF: 0.651 AC: 99032 AN: 152098 Hom.: 32992 Cov.: 32 AF XY: 0.642 AC XY: 47734 AN XY: 74336

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.658

Alfa AF: 0.563 Hom.: 2788

Bravo AF: 0.648

Asia WGS AF: 0.387 AC: 1349 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 45. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0020
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2111235; hg19: chr16-50733969; COSMIC: COSV56050565; COSMIC: COSV56050565;