NM_001040716.2(PC):c.2511_2531dup (p.Leu844_Tyr845insTrpGluGlyAlaArgGlyLeu) AND Pyruvate carboxylase deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 15, 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:: RCV002837604.3

Allele description [Variation Report for NM_001040716.2(PC):c.2511_2531dup (p.Leu844_Tyr845insTrpGluGlyAlaArgGlyLeu)]

NM_001040716.2(PC):c.2511_2531dup (p.Leu844_Tyr845insTrpGluGlyAlaArgGlyLeu)

Gene:

PC:pyruvate carboxylase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_001040716.2(PC):c.2511_2531dup (p.Leu844_Tyr845insTrpGluGlyAlaArgGlyLeu)

HGVS:

NC_000011.10:g.66850407_66850427dup
NG_008319.1:g.112950_112970dup
NG_123024.1:g.264_284dup
NM_000920.4:c.2511_2531dup
NM_001040716.2:c.2511_2531dupMANE SELECT
NM_022172.3:c.2511_2531dup
NP_000911.2:p.Leu844_Tyr845insTrpGluGlyAlaArgGlyLeu
NP_001035806.1:p.Leu844_Tyr845insTrpGluGlyAlaArgGlyLeu
NP_071504.2:p.Leu844_Tyr845insTrpGluGlyAlaArgGlyLeu
NC_000011.9:g.66617877_66617878insAGTCCCCGAGCCCCCTCCCAG
NC_000011.9:g.66617878_66617898dup

Molecular consequence:

NM_000920.4:c.2511_2531dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001040716.2:c.2511_2531dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_022172.3:c.2511_2531dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Name:: Pyruvate carboxylase deficiency
Synonyms:: ATAXIA WITH LACTIC ACIDOSIS II; PC deficiency; Ataxia with lactic acidosis 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009949; MedGen: C0034341; Orphanet: 3008; OMIM: 266150

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hypothetical protein LOC169355 [Homo sapiens]
hypothetical protein LOC169355 [Homo sapiens]
gi|34916024|ref|NP_919270.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003206534	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 15, 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

SCV003206534

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 15, 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, SCV003206534.2

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

Description

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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with PC-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.2511_2531dup, results in the insertion of 7 amino acid(s) of the PC protein (p.Trp838_Leu844dup), but otherwise preserves the integrity of the reading frame.

#	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

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