16-50724938-G-A

Position:

• chr16-50724938-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
NOD2	NM_001370466.1	c.2802-551G>A		intron_variant		ENST00000647318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD2	ENST00000647318.2	c.2802-551G>A		intron_variant			NM_001370466.1	P1

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

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.202

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

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

Other links and lift over

dbSNP: rs749910; hg19: chr16-50758849;