16-50717264-T-G

Variant names:

• chr16-50717264-T-G
• rs751271
• NM_001370466.1:c.2549+290T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001370466.1(NOD2):​c.2549+290T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,140 control chromosomes in the GnomAD database, including 28,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28852 hom., cov: 33)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.136
• Publications: 24 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-50717264-T-G is Benign according to our data. Variant chr16-50717264-T-G is described in ClinVar as Benign. ClinVar VariationId is 1256923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.2549+290T>G		intron_variant	Intron 6 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.2549+290T>G		intron_variant	Intron 6 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92137 AN: 152022 Hom.: 28839 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.606 AC: 92194 AN: 152140 Hom.: 28852 Cov.: 33 AF XY: 0.596 AC XY: 44355 AN XY: 74366

African (AFR) AF: 0.585 AC: 24269 AN: 41486

American (AMR) AF: 0.565 AC: 8636 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2692 AN: 3466

East Asian (EAS) AF: 0.195 AC: 1012 AN: 5180

South Asian (SAS) AF: 0.351 AC: 1694 AN: 4822

European-Finnish (FIN) AF: 0.571 AC: 6037 AN: 10576

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45666 AN: 67998

Other (OTH) AF: 0.622 AC: 1314 AN: 2114

Alfa AF: 0.615 Hom.: 10373

Bravo AF: 0.605

Asia WGS AF: 0.297 AC: 1037 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.48
PhyloP100		0.14
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: rs751271; hg19: chr16-50751175;