NM_024884.3(L2HGDH):c.68C>A (p.Ser23Tyr) AND L-2-hydroxyglutaric aciduria

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 22, 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:: RCV003090984.10

Allele description [Variation Report for NM_024884.3(L2HGDH):c.68C>A (p.Ser23Tyr)]

NM_024884.3(L2HGDH):c.68C>A (p.Ser23Tyr)

Genes:

L2HGDH:L-2-hydroxyglutarate dehydrogenase [Gene - OMIM - HGNC]
DMAC2L:distal membrane arm assembly component 2 like [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q21.3

Genomic location:

Preferred name:

NM_024884.3(L2HGDH):c.68C>A (p.Ser23Tyr)

HGVS:

NC_000014.9:g.50312083G>T
NG_008092.1:g.5147C>A
NM_001382509.1:c.-6+229G>T
NM_001425212.1:c.68C>A
NM_001425213.1:c.-187C>A
NM_001425214.1:c.-187C>A
NM_001425215.1:c.-701C>A
NM_001425216.1:c.-543C>A
NM_001425217.1:c.-636C>A
NM_001425218.1:c.-558C>A
NM_024884.3:c.68C>AMANE SELECT
NP_001412141.1:p.Ser23Tyr
NP_079160.1:p.Ser23Tyr
NC_000014.8:g.50778801G>T

Protein change:

S23Y

Molecular consequence:

NM_001425213.1:c.-187C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001425214.1:c.-187C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001425215.1:c.-701C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001425216.1:c.-543C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001425217.1:c.-636C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001425218.1:c.-558C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001382509.1:c.-6+229G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001425212.1:c.68C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024884.3:c.68C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: L-2-hydroxyglutaric aciduria (L2HGA)
Identifiers:: MONDO: MONDO:0009370; MedGen: C1855995; Orphanet: 79314; OMIM: 236792; Human Phenotype Ontology: HP:0040144

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003467878	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 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

SCV003467878

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 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, SCV003467878.2

#	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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with L2HGDH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 23 of the L2HGDH protein (p.Ser23Tyr).

#	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: Nov 30, 2024

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