NM_000520.6(HEXA):c.1168del (p.Gln390fs) AND Tay-Sachs disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 17, 2023
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:: RCV001941601.4

Allele description [Variation Report for NM_000520.6(HEXA):c.1168del (p.Gln390fs)]

NM_000520.6(HEXA):c.1168del (p.Gln390fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

15q23

Genomic location:

Preferred name:

NM_000520.6(HEXA):c.1168del (p.Gln390fs)

HGVS:

NC_000015.10:g.72346689del
NG_009017.2:g.34491del
NM_000520.6:c.1168delMANE SELECT
NM_001318825.2:c.1201del
NP_000511.2:p.Gln390fs
NP_001305754.1:p.Gln401fs
NC_000015.9:g.72639030del

Protein change:

Q390fs

Links:

dbSNP: rs772879726

NCBI 1000 Genomes Browser:

rs772879726

Molecular consequence:

NM_000520.6:c.1168del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001318825.2:c.1201del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Tay-Sachs disease (TSD)
Synonyms:: GM2 gangliosidosis, type 1; HexA deficiency; Hexosaminidase alpha-subunit deficiency (variant B); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010100; MedGen: C0039373; Orphanet: 845; OMIM: 272800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002233200	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 1833974, 8490625, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002233200

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 17, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease.

Triggs-Raine BL, Akerman BR, Clarke JT, Gravel RA.

Am J Hum Genet. 1991 Nov;49(5):1041-54.

PubMed [citation]

PMID:: 1833974
PMCID:: PMC1683266

Ten novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients.

Akli S, Chomel JC, Lacorte JM, Bachner L, Kahn A, Poenaru L.

Hum Mol Genet. 1993 Jan;2(1):61-7. Erratum in: Hum Mol Genet 1993 Apr;2(4):496.

PubMed [citation]

PMID:: 8490625

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002233200.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln390Argfs*9) in the HEXA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). This variant is present in population databases (rs772879726, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with HEXA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1453891). 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

Last Updated: Sep 29, 2024

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Relating variation to medicine