NM_001625.4(AK2):c.499-1_499insATGAC (p.Ile167fs) AND Severe combined immunodeficiency disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 11, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001825069.1

Allele description [Variation Report for NM_001625.4(AK2):c.499-1_499insATGAC (p.Ile167fs)]

NM_001625.4(AK2):c.499-1_499insATGAC (p.Ile167fs)

Gene:

AK2:adenylate kinase 2 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

1p35.1

Genomic location:

Preferred name:

NM_001625.4(AK2):c.499-1_499insATGAC (p.Ile167fs)

HGVS:

NC_000001.11:g.33013402_33013403insGTCAT
NG_016269.1:g.28491_28492insGACAT
NM_001199199.3:c.475-1_475insATGAC
NM_001319139.3:c.355-1_355insATGAC
NM_001319140.2:c.355-1_355insATGAC
NM_001319141.3:c.499-1_499insATGAC
NM_001319142.3:c.373-1_373insATGAC
NM_001319143.2:c.*2-1_*2insATGAC
NM_001625.4:c.499-1_499insATGACMANE SELECT
NM_013411.5:c.499-1_499insATGAC
NP_001186128.1:p.Ile159fs
NP_001306068.1:p.Ile119fs
NP_001306069.1:p.Ile119fs
NP_001306070.1:p.Ile167fs
NP_001306071.1:p.Ile125fs
NP_001306072.1:p.Arg133_Ter134=
NP_001616.1:p.Ile167fs
NP_037543.1:p.Ile167(?)
NP_037543.1:p.Ile167fs
LRG_133t1:c.499-1_499insATGAC
LRG_133:g.28491_28492insGACAT
LRG_133p1:p.Ile167(?)
NC_000001.10:g.33479003_33479004insGTCAT
NM_001625.3:c.500_501insGACAT
NM_013411.3:c.499-1_499insATGAC
NR_037591.1:n.700-1_700insATGAC
NR_037592.1:n.700-1_700insATGAC
NR_134976.3:n.459-1_459insATGAC

Protein change:

I119fs

Links:

dbSNP: rs1398317449

NCBI 1000 Genomes Browser:

rs1398317449

Molecular consequence:

NM_001199199.3:c.475-1_475insATGAC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319139.3:c.355-1_355insATGAC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319140.2:c.355-1_355insATGAC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319141.3:c.499-1_499insATGAC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319142.3:c.373-1_373insATGAC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001625.4:c.499-1_499insATGAC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_013411.5:c.499-1_499insATGAC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319143.2:c.*2-1_*2insATGAC - no sequence alteration - [Sequence Ontology: SO:0002073]
NR_134976.3:n.459-1_459insATGAC - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Severe combined immunodeficiency disease (SCID)
Synonyms:: Severe combined immunodeficiency; Bubble boy disease; Severe Combined Immune Deficiency
Identifiers:: MONDO: MONDO:0015974; MeSH: D016511; MedGen: C0085110; Human Phenotype Ontology: HP:0004430

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002074208	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jan 11, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002074208

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jan 11, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002074208.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: AK2 c.500_501insGACAT (p.Ile167MetfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in HGMD in association with Reticular dysgenesis (p.Gly205Aspfs*28, p.Ser213Aspfs*21). The variant allele was found at a frequency of 4e-06 in 249484 control chromosomes. To our knowledge, no occurrence of c.500_501insGACAT in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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