rs749910

Variant names:

• chr16-50724938-G-A
• rs749910
• NM_001370466.1:c.2802-551G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370466.1(NOD2):​c.2802-551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,210 control chromosomes in the GnomAD database, including 2,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2868 hom., cov: 33)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 3 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.2802-551G>A		intron_variant	Intron 9 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.2802-551G>A		intron_variant	Intron 9 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25739 AN: 152092 Hom.: 2868 Cov.: 33

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25742 AN: 152210 Hom.: 2868 Cov.: 33 AF XY: 0.164 AC XY: 12219 AN XY: 74416

African (AFR) AF: 0.0528 AC: 2192 AN: 41542

American (AMR) AF: 0.158 AC: 2414 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3468

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5190

South Asian (SAS) AF: 0.129 AC: 620 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1611 AN: 10590

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17271 AN: 67982

Other (OTH) AF: 0.202 AC: 427 AN: 2110

Alfa AF: 0.202 Hom.: 458

Bravo AF: 0.163

Asia WGS AF: 0.0710 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.6
DANN	Benign	0.72
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs749910; hg19: chr16-50758849;