NM_001625.4(AK2):c.470A>G (p.Asn157Ser) AND Reticular dysgenesis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 16, 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:: RCV000797068.6

Allele description [Variation Report for NM_001625.4(AK2):c.470A>G (p.Asn157Ser)]

NM_001625.4(AK2):c.470A>G (p.Asn157Ser)

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.470A>G (p.Asn157Ser)

HGVS:

NC_000001.11:g.33014550T>C
NG_016269.1:g.27342A>G
NM_001199199.3:c.446A>G
NM_001319139.3:c.326A>G
NM_001319140.2:c.326A>G
NM_001319141.3:c.470A>G
NM_001319142.3:c.344A>G
NM_001319143.2:c.375A>G
NM_001625.4:c.470A>GMANE SELECT
NM_013411.5:c.470A>G
NP_001186128.1:p.Asn149Ser
NP_001306068.1:p.Asn109Ser
NP_001306069.1:p.Asn109Ser
NP_001306070.1:p.Asn157Ser
NP_001306071.1:p.Asn115Ser
NP_001306072.1:p.Gln125=
NP_001616.1:p.Asn157Ser
NP_037543.1:p.Asn157Ser
LRG_133:g.27342A>G
NC_000001.10:g.33480151T>C
NM_001625.3:c.470A>G
NR_134976.3:n.430A>G

Protein change:

N109S

Links:

dbSNP: rs371672441

NCBI 1000 Genomes Browser:

rs371672441

Molecular consequence:

NM_001199199.3:c.446A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319139.3:c.326A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319140.2:c.326A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319141.3:c.470A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001319142.3:c.344A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001625.4:c.470A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_013411.5:c.470A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_134976.3:n.430A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001319143.2:c.375A>G - synonymous variant - [Sequence Ontology: SO:0001819]

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
SCV000936608	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 16, 2022)	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

SCV000936608

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 16, 2022)

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, SCV000936608.3

#	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, which is neutral and polar, with serine, which is neutral and polar, at codon 157 of the AK2 protein (p.Asn157Ser). This variant is present in population databases (rs371672441, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with AK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 643382). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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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