NM_000170.3(GLDC):c.2423_2426dup (p.Ile810fs) AND Non-ketotic hyperglycinemia

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Sep 16, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000586601.5

Allele description [Variation Report for NM_000170.3(GLDC):c.2423_2426dup (p.Ile810fs)]

NM_000170.3(GLDC):c.2423_2426dup (p.Ile810fs)

Gene:
GLDC:glycine decarboxylase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
9p24.1
Genomic location:
Preferred name:
NM_000170.3(GLDC):c.2423_2426dup (p.Ile810fs)
HGVS:
  • NC_000009.12:g.6553399_6553402dup
  • NG_016397.1:g.97291_97294dup
  • NM_000170.3:c.2423_2426dupMANE SELECT
  • NP_000161.2:p.Ile810fs
  • LRG_643:g.97291_97294dup
  • NC_000009.11:g.6553398_6553399insGAAC
  • NC_000009.11:g.6553399_6553402dup
  • NM_000170.2:c.2423_2426dupGTTC
Protein change:
I810fs
Links:
dbSNP: rs755313904
NCBI 1000 Genomes Browser:
rs755313904
Molecular consequence:
  • NM_000170.3:c.2423_2426dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Non-ketotic hyperglycinemia (GCE)
Synonyms:
Glycine encephalopathy; Nonketotic hyperglycinemia
Identifiers:
MONDO: MONDO:0011612; MedGen: C0751748; Orphanet: 407; OMIM: 605899; Human Phenotype Ontology: HP:0008288

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000695758Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Feb 11, 2016)
germlineclinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001580888Invitaecriteria provided, single submitter
Pathogenic
(Sep 16, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Genetic heterogeneity of the GLDC gene in 28 unrelated patients with glycine encephalopathy.

Conter C, Rolland MO, Cheillan D, Bonnet V, Maire I, Froissart R.

J Inherit Metab Dis. 2006 Feb;29(1):135-42.

PubMed [citation]
PMID:
16601880

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695758.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001580888.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Ile810Phefs*19) in the GLDC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs755313904, ExAC 0.001%). This variant has not been reported in the literature in individuals with GLDC-related conditions. ClinVar contains an entry for this variant (Variation ID: 495699). Loss-of-function variants in GLDC are known to be pathogenic (PMID: 16601880). 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: Oct 25, 2021

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