rs5743271

Variant names:

• chr16-50710777-A-C
• NM_001370466.1:c.785A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-50710777-A-C
• chr16-50710777-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370466.1(NOD2):​c.785A>C​(p.Asn262Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N262S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NOD2 NM_001370466.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.18

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28859335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.785A>C	p.Asn262Thr	missense_variant	Exon 4 of 12	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.785A>C	p.Asn262Thr	missense_variant	Exon 4 of 12		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461836 Hom.: 0 Cov.: 40 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Uncertain	0.43	.;T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.29	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Uncertain	-0.039	T
MutationAssessor	Pathogenic	3.2	.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.7	.;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0060	.;D
Polyphen		0.99	D;P
Vest4		0.49
MutPred		0.26		.;Gain of phosphorylation at N289 (P = 0.0287);
MVP		0.81
MPC		0.41
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.38
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-50744688;