rs1555718890

Variant names:

• chr19-10362461-CA-AG
• rs1555718890
• NM_003331.5:c.1477-6_1477-5delTGinsCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_003331.5(TYK2):​c.1477-6_1477-5delTGinsCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TYK2 NM_003331.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.62
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 19-10362461-CA-AG is Benign according to our data. Variant chr19-10362461-CA-AG is described in ClinVar as Likely_benign. ClinVar VariationId is 536651.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYK2	NM_003331.5	MANE Select	c.1477-6_1477-5delTGinsCT		splice_region intron	N/A	NP_003322.3
	TYK2	NM_001385204.1		c.1477-6_1477-5delTGinsCT		splice_region intron	N/A	NP_001372133.1
	TYK2	NM_001385203.1		c.1477-6_1477-5delTGinsCT		splice_region intron	N/A	NP_001372132.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYK2	ENST00000525621.6	TSL:1 MANE Select	c.1477-6_1477-5delTGinsCT		splice_region intron	N/A	ENSP00000431885.1
	TYK2	ENST00000524462.5	TSL:1	c.922-6_922-5delTGinsCT		splice_region intron	N/A	ENSP00000433203.1
	TYK2	ENST00000531836.7	TSL:4	c.1477-6_1477-5delTGinsCT		splice_region intron	N/A	ENSP00000436175.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 35 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.6

Splicing

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

Other links and lift over

dbSNP: rs1555718890; hg19: chr19-10473137;