NM_001243177.4(ALDOA):c.803A>G (p.Tyr268Cys) AND HNSHA due to aldolase A deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 2023
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:: RCV003067244.2

Allele description [Variation Report for NM_001243177.4(ALDOA):c.803A>G (p.Tyr268Cys)]

NM_001243177.4(ALDOA):c.803A>G (p.Tyr268Cys)

Genes:

ALDOA:aldolase, fructose-bisphosphate A [Gene - OMIM - HGNC]
LOC112694756:uncharaterized LOC112694756 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_001243177.4(ALDOA):c.803A>G (p.Tyr268Cys)

HGVS:

NC_000016.10:g.30069515A>G
NG_008010.1:g.21346A>G
NM_001127617.2:c.641A>G
NM_001243177.4:c.803A>GMANE SELECT
NM_001365304.2:c.*1150A>GMANE SELECT
NM_001365305.2:c.*1150A>G
NM_001365307.2:c.*1150A>G
NM_184041.5:c.641A>G
NM_184043.2:c.641A>G
NP_001121089.1:p.Tyr214Cys
NP_001230106.1:p.Tyr268Cys
NP_908930.1:p.Tyr214Cys
NP_908932.1:p.Tyr214Cys
LRG_1180t1:c.641A>G
LRG_1180t2:c.803A>G
LRG_1180:g.21346A>G
LRG_1180p1:p.Tyr214Cys
LRG_1180p2:p.Tyr268Cys
NC_000016.9:g.30080836A>G

Protein change:

Y214C

Molecular consequence:

NM_001365304.2:c.*1150A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001365305.2:c.*1150A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001365307.2:c.*1150A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001127617.2:c.641A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001243177.4:c.803A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_184041.5:c.641A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_184043.2:c.641A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: HNSHA due to aldolase A deficiency (GSD12)
Synonyms:: GLYCOGEN STORAGE DISEASE XII; GSD XII; Glycogen storage disease type 12; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012747; MedGen: C0272066; Orphanet: 57; OMIM: 611881

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003453910	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 10, 2023)	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

SCV003453910

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 10, 2023)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003453910.2

#	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 tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 214 of the ALDOA protein (p.Tyr214Cys). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ALDOA-related conditions. ClinVar contains an entry for this variant (Variation ID: 2146663). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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: Feb 28, 2024

ClinVar

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