NM_001040716.2(PC):c.2493_2494del (p.Val831_Phe832insTer) AND Pyruvate carboxylase deficiency

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Dec 29, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000672343.10

Allele description [Variation Report for NM_001040716.2(PC):c.2493_2494del (p.Val831_Phe832insTer)]

NM_001040716.2(PC):c.2493_2494del (p.Val831_Phe832insTer)

Gene:

PC:pyruvate carboxylase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_001040716.2(PC):c.2493_2494del (p.Val831_Phe832insTer)

HGVS:

NC_000011.10:g.66850444AC[1]
NG_008319.1:g.112930GT[1]
NM_000920.4:c.2493_2494del
NM_001040716.2:c.2493_2494delMANE SELECT
NM_022172.3:c.2493_2494del
NP_000911.2:p.Val831_Phe832insTer
NP_001035806.1:p.Val831_Phe832insTer
NP_071504.2:p.Val831_Phe832insTer
NC_000011.9:g.66617915AC[1]
NC_000011.9:g.66617915_66617916del
NM_000920.3:c.2493_2494delGT

Links:

OMIM: 608786.0006; dbSNP: rs756355930

NCBI 1000 Genomes Browser:

rs756355930

Molecular consequence:

NM_000920.4:c.2493_2494del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001040716.2:c.2493_2494del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_022172.3:c.2493_2494del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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Gm15030 AND (alive[prop]) (2)
Gene
UREG_07371 [Uncinocarpus reesii 1704]
UREG_07371 [Uncinocarpus reesii 1704]
Gene ID:8439972

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022338	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000797440	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Pathogenic (Jan 25, 2018)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18676167, 12112657 Citation Link,
SCV001585412	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 29, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19306334, 12112657, 18676167, 28492532
SCV004202826	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 5, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency.

Monnot S, Serre V, Chadefaux-Vekemans B, Aupetit J, Romano S, De Lonlay P, Rival JM, Munnich A, Steffann J, Bonnefont JP.

Hum Mutat. 2009 May;30(5):734-40. doi: 10.1002/humu.20908.

PubMed [citation]

PMID:: 19306334

Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings.

Carbone MA, Applegarth DA, Robinson BH.

Hum Mutat. 2002 Jul;20(1):48-56.

PubMed [citation]

PMID:: 12112657

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000022338.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the dinucleotide deletion in exon 16 (2491_2492delGT) of the PC gene that was found in compound heterozygous state in 2 brothers with severe (type B) pyruvate carboxylase deficiency (266150) by Carbone et al. (2002), see (608786.0005).

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

From Counsyl, SCV000797440.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001585412.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Phe832*) in the PC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PC are known to be pathogenic (PMID: 12112657, 19306334). This variant is present in population databases (rs756355930, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with pyruvate carboxylase deficiency (PMID: 12112657, 18676167). This variant is also known as 2491-2492delGT. ClinVar contains an entry for this variant (Variation ID: 556347). For these reasons, this variant has been classified as Pathogenic.

#	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

From Baylor Genetics, SCV004202826.1

#	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

Last Updated: Sep 29, 2024

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