rs2304259

Variant names:

• chr19-10380676-T-G
• rs2304259
• NM_003331.5:c.-482A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003331.5(TYK2):​c.-482A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 150,928 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00013 (1 hom., cov: 30)
  • Exomes 𝑓: 0.022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TYK2 NM_003331.5 upstream_gene
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.87

Genes affected

TYK2 (HGNC:12440): (tyrosine kinase 2) This gene encodes a member of the tyrosine kinase and, more specifically, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. A mutation in this gene has been associated with Immunodeficiency 35. [provided by RefSeq, Sep 2020]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYK2	NM_003331.5	c.-482A>C		upstream_gene_variant		ENST00000525621.6	NP_003322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYK2	ENST00000525621.6	c.-482A>C		upstream_gene_variant		1	NM_003331.5	ENSP00000431885.1

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 20 AN: 150824 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000785

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.000195

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000965

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0217 AC: 2 AN: 92 Hom.: 0 Cov.: 0 AF XY: 0.0323 AC XY: 2 AN XY: 62

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.0625

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.000133 AC: 20 AN: 150928 Hom.: 1 Cov.: 30 AF XY: 0.000149 AC XY: 11 AN XY: 73644

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000659

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000787

Gnomad4 SAS AF: 0.000627

Gnomad4 FIN AF: 0.000195

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000956

Alfa AF: 0.103 Hom.: 327

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Virus-induced diabetes Uncertain:1

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Division of Host Defense, Kyushu University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.48
DANN	Benign	0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2304259; hg19: chr19-10491352;