NM_000520.6(HEXA):c.1073+1G>C AND Tay-Sachs disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 14, 2020
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:: RCV001390151.7

Allele description [Variation Report for NM_000520.6(HEXA):c.1073+1G>C]

NM_000520.6(HEXA):c.1073+1G>C

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.1073+1G>C

HGVS:

NC_000015.10:g.72348047C>G
NG_009017.2:g.33133G>C
NG_009017.3:g.32967G>C
NM_000520.6:c.1073+1G>CMANE SELECT
NM_001318825.2:c.1106+1G>C
NC_000015.9:g.72640388C>G

Links:

dbSNP: rs76173977

NCBI 1000 Genomes Browser:

rs76173977

Molecular consequence:

NM_000520.6:c.1073+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001318825.2:c.1106+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001591786	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 14, 2020)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 1301938, 8444467, 16199547, 1833974, 8490625, 1387685, 19858779, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591786

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 14, 2020)

germline

clinical testing

PubMed (8)
[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

A mutation common in non-Jewish Tay-Sachs disease: frequency and RNA studies.

Akerman BR, Zielenski J, Triggs-Raine BL, Prence EM, Natowicz MR, Lim-Steele JS, Kaback MM, Mules EH, Thomas GH, Clarke JT, et al.

Hum Mutat. 1992;1(4):303-9.

PubMed [citation]

PMID:: 1301938

A null allele frequent in non-Jewish Tay-Sachs patients.

Akli S, Chelly J, Kahn A, Poenaru L.

Hum Genet. 1993 Feb;90(6):614-20.

PubMed [citation]

PMID:: 8444467

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591786.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

Experimental studies have shown that this disruption of this splice site affects mRNA splicing (PMID: 1301938, 8444467). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HEXA are known to be pathogenic (PMID: 1833974, 8490625). Disruption of this splice site has been observed in individual(s) with Tay-Sachs disease (PMID: 8490625, 1387685, 19858779). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 9 of the HEXA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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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