Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4

The NM_003331.5(TYK2):c.386_391delGAACCG(p.Gly129_Thr130del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

TYK2
NM_003331.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.558

Publications

0 publications found

Variant links:

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)

TYK2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_003331.5.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TYK2	NM_003331.5	MANE Select	c.386_391delGAACCG	p.Gly129_Thr130del	disruptive_inframe_deletion	Exon 5 of 25	NP_003322.3
TYK2	NM_001385204.1		c.386_391delGAACCG	p.Gly129_Thr130del	disruptive_inframe_deletion	Exon 5 of 25	NP_001372133.1
TYK2	NM_001385203.1		c.386_391delGAACCG	p.Gly129_Thr130del	disruptive_inframe_deletion	Exon 5 of 26	NP_001372132.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TYK2	ENST00000525621.6	TSL:1 MANE Select	c.386_391delGAACCG	p.Gly129_Thr130del	disruptive_inframe_deletion	Exon 5 of 25	ENSP00000431885.1
TYK2	ENST00000524462.5	TSL:1	c.-90-1554_-90-1549delGAACCG		intron	N/A	ENSP00000433203.1
TYK2	ENST00000531836.7	TSL:4	c.386_391delGAACCG	p.Gly129_Thr130del	disruptive_inframe_deletion	Exon 5 of 25	ENSP00000436175.2

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 35 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.56

Splicing

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

Publications

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rs1555720565

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over