NM_001625.4(AK2):c.471C>G (p.Asn157Lys) AND Reticular dysgenesis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2021
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:: RCV000810946.6

Allele description [Variation Report for NM_001625.4(AK2):c.471C>G (p.Asn157Lys)]

NM_001625.4(AK2):c.471C>G (p.Asn157Lys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p35.1

Genomic location:

Preferred name:

NM_001625.4(AK2):c.471C>G (p.Asn157Lys)

HGVS:

NC_000001.11:g.33014549G>C
NG_016269.1:g.27343C>G
NM_001199199.3:c.447C>G
NM_001319139.3:c.327C>G
NM_001319140.2:c.327C>G
NM_001319141.3:c.471C>G
NM_001319142.3:c.345C>G
NM_001319143.2:c.376C>G
NM_001625.4:c.471C>GMANE SELECT
NM_013411.5:c.471C>G
NP_001186128.1:p.Asn149Lys
NP_001306068.1:p.Asn109Lys
NP_001306069.1:p.Asn109Lys
NP_001306070.1:p.Asn157Lys
NP_001306071.1:p.Asn115Lys
NP_001306072.1:p.Pro126Ala
NP_001616.1:p.Asn157Lys
NP_037543.1:p.Asn157Lys
LRG_133:g.27343C>G
NC_000001.10:g.33480150G>C
NM_001625.3:c.471C>G
NR_134976.3:n.431C>G

Protein change:

N109K

Links:

dbSNP: rs146442876

NCBI 1000 Genomes Browser:

rs146442876

Molecular consequence:

NM_001199199.3:c.447C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319139.3:c.327C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319140.2:c.327C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319141.3:c.471C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319142.3:c.345C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319143.2:c.376C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001625.4:c.471C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_013411.5:c.471C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_134976.3:n.431C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Reticular dysgenesis
Synonyms:: ALEUKOCYTOSIS; HEMATOPOIETIC HYPOPLASIA, GENERALIZED; RETICULAR DYSGENESIA; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009973; MedGen: C0272167; Orphanet: 33355; OMIM: 267500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000951188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000951188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000951188.3

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

Description

This sequence change replaces asparagine with lysine at codon 157 of the AK2 protein (p.Asn157Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs146442876, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with AK2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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