NM_001625.4(AK2):c.5C>T (p.Ala2Val) AND Reticular dysgenesis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 30, 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:: RCV001936413.4

Allele description [Variation Report for NM_001625.4(AK2):c.5C>T (p.Ala2Val)]

NM_001625.4(AK2):c.5C>T (p.Ala2Val)

Genes:

LOC129930068:ATAC-STARR-seq lymphoblastoid active region 705 [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.5C>T (p.Ala2Val)

HGVS:

NC_000001.11:g.33036824G>A
NG_016269.1:g.5068C>T
NM_001199199.3:c.5C>T
NM_001319139.3:c.-258C>T
NM_001319140.2:c.-258C>T
NM_001319141.3:c.5C>T
NM_001319142.3:c.5C>T
NM_001319143.2:c.5C>T
NM_001625.4:c.5C>TMANE SELECT
NM_013411.5:c.5C>T
NP_001186128.1:p.Ala2Val
NP_001306070.1:p.Ala2Val
NP_001306071.1:p.Ala2Val
NP_001306072.1:p.Ala2Val
NP_001616.1:p.Ala2Val
NP_037543.1:p.Ala2Val
LRG_133:g.5068C>T
NC_000001.10:g.33502425G>A
NR_134976.3:n.60C>T

Protein change:

A2V

Links:

dbSNP: rs1394062153

NCBI 1000 Genomes Browser:

rs1394062153

Molecular consequence:

NM_001319139.3:c.-258C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001319140.2:c.-258C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001199199.3:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001319141.3:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001319142.3:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001319143.2:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001625.4:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_013411.5:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_134976.3:n.60C>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002197673	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 30, 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

SCV002197673

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 30, 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, SCV002197673.3

#	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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the AK2 protein (p.Ala2Val). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1428648). This variant has not been reported in the literature in individuals affected with AK2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.

#	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

ClinVar

Relating variation to medicine