NM_000520.6(HEXA):c.533G>A (p.Arg178His) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 16, 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:: RCV000396083.36

Allele description [Variation Report for NM_000520.6(HEXA):c.533G>A (p.Arg178His)]

NM_000520.6(HEXA):c.533G>A (p.Arg178His)

Gene:

HEXA:hexosaminidase subunit alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q23

Genomic location:

Preferred name:

NM_000520.6(HEXA):c.533G>A (p.Arg178His)

HGVS:

NC_000015.10:g.72353105C>T
NG_009017.2:g.28075G>A
NM_000520.5:c.533G>A
NM_000520.6:c.533G>AMANE SELECT
NM_000520.6:c.533G>A
NM_001318825.2:c.566G>A
NP_000511.2:p.Arg178His
NP_001305754.1:p.Arg189His
NC_000015.9:g.72645446C>T
NM_000520.4:c.533G>A
NR_134869.3:n.575G>A
P06865:p.Arg178His

Protein change:

R178H; ARG178HIS

Links:

UniProtKB: P06865#VAR_003209; OMIM: 606869.0006; dbSNP: rs28941770

NCBI 1000 Genomes Browser:

rs28941770

Molecular consequence:

NM_000520.6:c.533G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318825.2:c.566G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134869.3:n.575G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329360	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 16, 2023)	germline	clinical testing	Citation Link,
SCV000854794	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Dec 4, 2017)	germline	clinical testing	Citation Link,
SCV001249190	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329360

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Nov 16, 2023)

germline

clinical testing

Citation Link,

SCV000854794

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Dec 4, 2017)

germline

clinical testing

Citation Link,

SCV001249190

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Jul 1, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	4	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000329360.10

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

Description

Common pathogenic variant identified in Spanish, Portuguese, and Italian populations and is associated with late-onset Tay Sachs disease (PMID: 22789865); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22975760, 2521932, 1318511, 21228398, 26286102, 34712575, 10584247, 2973311, 28923328, 16088929, 2961848, 27362553, 1832817, 34440436, 32005694, 31589614, 33240792, 33258288, 18490185, 22789865, 2137287)

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

From Eurofins Ntd Llc (ga), SCV000854794.1

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

#	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		4	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001249190.27

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

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

Last Updated: Jan 13, 2025

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