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NM_000187.4(HGD):c.1188+2T>A AND Alkaptonuria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 13, 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:
RCV002953408.2

Allele description [Variation Report for NM_000187.4(HGD):c.1188+2T>A]

NM_000187.4(HGD):c.1188+2T>A

Gene:
HGD:homogentisate 1,2-dioxygenase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q13.33
Genomic location:
Preferred name:
NM_000187.4(HGD):c.1188+2T>A
HGVS:
  • NC_000003.12:g.120633145A>T
  • NG_011957.1:g.54337T>A
  • NM_000187.4:c.1188+2T>AMANE SELECT
  • NC_000003.11:g.120351992A>T
Molecular consequence:
  • NM_000187.4:c.1188+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Alkaptonuria (AKU)
Synonyms:
Alcaptonuria; Ochronosis, hereditary; Homogentisic acid oxidase deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008753; MedGen: C0002066; Orphanet: 56; OMIM: 203500

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003274396Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 13, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003274396.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change affects a donor splice site in intron 13 of the HGD gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HGD-related conditions. 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. This variant disrupts a region of the HGD protein in which other variant(s) (p.Lys431Hisfs*11) have been determined to be pathogenic (PMID: 23430897, 25681086). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024