NM_001365304.2(LOC112694756):c.*1309-2dup AND HNSHA due to aldolase A deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 2, 2024
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:: RCV002957640.2

Allele description [Variation Report for NM_001365304.2(LOC112694756):c.*1309-2dup]

NM_001365304.2(LOC112694756):c.*1309-2dup

Genes:

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

Variant type:

Duplication

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_001365304.2(LOC112694756):c.*1309-2dup

HGVS:

NC_000016.10:g.30069828dup
NG_008010.1:g.21659dup
NM_001127617.2:c.800-2dup
NM_001243177.4:c.962-2dupMANE SELECT
NM_001365304.2:c.*1309-2dupMANE SELECT
NM_001365305.2:c.*1309-2dup
NM_001365307.2:c.*1309-2dup
NM_184041.5:c.800-2dup
NM_184043.2:c.800-2dup
LRG_1180t1:c.800-2dup
LRG_1180t2:c.962-2dup
LRG_1180:g.21659dup
NC_000016.9:g.30081148_30081149insA
NC_000016.9:g.30081149dup

Molecular consequence:

NM_001127617.2:c.800-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001243177.4:c.962-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001365304.2:c.*1309-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001365305.2:c.*1309-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001365307.2:c.*1309-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_184041.5:c.800-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_184043.2:c.800-2dup - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV003271393	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 2, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003271393

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 2, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003271393.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change falls in intron 12 of the ALDOA gene. It does not directly change the encoded amino acid sequence of the ALDOA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs775439610, gnomAD 0.006%). 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: 2060274). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 20, 2024

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