NM_000284.4(PDHA1):c.292-23A>G AND Pyruvate dehydrogenase E1-alpha deficiency

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 8, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000415131.7

Allele description [Variation Report for NM_000284.4(PDHA1):c.292-23A>G]

NM_000284.4(PDHA1):c.292-23A>G

Gene:

PDHA1:pyruvate dehydrogenase E1 subunit alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp22.12

Genomic location:

Preferred name:

NM_000284.4(PDHA1):c.292-23A>G

HGVS:

NC_000023.11:g.19351258A>G
NG_016781.1:g.12366A>G
NM_000284.4:c.292-23A>GMANE SELECT
NM_001173454.2:c.406-23A>G
NM_001173455.2:c.292-2A>G
NM_001173456.2:c.292-23A>G
NC_000023.10:g.19369376A>G

Links:

dbSNP: rs1057518702

NCBI 1000 Genomes Browser:

rs1057518702

Molecular consequence:

NM_000284.4:c.292-23A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001173454.2:c.406-23A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001173456.2:c.292-23A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001173455.2:c.292-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Pyruvate dehydrogenase E1-alpha deficiency (PDHAD)
Synonyms:: X-linked Leigh syndrome; ATAXIA, INTERMITTENT, WITH PYRUVATE DEHYDROGENASE DEFICIENCY; ATAXIA WITH LACTIC ACIDOSIS I; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010717; MedGen: C1839413; OMIM: 312170

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000328810	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001599354	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Nov 8, 2021)	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

SCV000328810

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001599354

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Nov 8, 2021)

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 Baylor Genetics, SCV000328810.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001599354.3

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

#	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 14, 2024

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