TYK2 p.Pro616Pro

Variant names:

• chr19-10361880-C-C
• NM_003331.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr19-10361881--
• chr19-10361881-A-G
• chr19-10361881-A-T
• chr19-10361881-A-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003331.5(TYK2):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYK2 NM_003331.5 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 0 publications found

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]

TYK2 Gene-Disease associations (from GenCC):

• immunodeficiency 35

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003331.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYK2	NM_003331.5	MANE Select	c.		exon_region	Exon 13 of 25	NP_003322.3
	TYK2	NM_001385204.1		c.		exon_region	Exon 13 of 25	NP_001372133.1
	TYK2	NM_001385203.1		c.		exon_region	Exon 13 of 26	NP_001372132.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYK2	ENST00000525621.6	TSL:1 MANE Select	c.		exon_region	Exon 13 of 25	ENSP00000431885.1	P29597
	TYK2	ENST00000524462.5	TSL:1	c.		exon_region	Exon 9 of 21	ENSP00000433203.1	E9PM19
	TYK2	ENST00000531836.7	TSL:4	c.		exon_region	Exon 13 of 25	ENSP00000436175.2	P29597

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-10472556;