NM_000520.6(HEXA):c.1039_1056del (p.Asp347_Glu352del) AND Tay-Sachs disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 31, 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:: RCV003226682.1

Allele description [Variation Report for NM_000520.6(HEXA):c.1039_1056del (p.Asp347_Glu352del)]

NM_000520.6(HEXA):c.1039_1056del (p.Asp347_Glu352del)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

15q23

Genomic location:

Preferred name:

NM_000520.6(HEXA):c.1039_1056del (p.Asp347_Glu352del)

HGVS:

NC_000015.10:g.72348068_72348085del
NG_009017.2:g.33098_33115del
NG_009017.3:g.32932_32949del
NM_000520.6:c.1039_1056delMANE SELECT
NM_001318825.2:c.1072_1089del
NP_000511.2:p.Asp347_Glu352del
NP_001305754.1:p.Asp358_Glu363del
NC_000015.9:g.72640409_72640426del
NM_000520.5:c.1039_1056del18
NR_134869.3:n.1081_1098del

Molecular consequence:

NM_000520.6:c.1039_1056del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001318825.2:c.1072_1089del - inframe_deletion - [Sequence Ontology: SO:0001822]
NR_134869.3:n.1081_1098del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

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Neobacillus piezotolerans strain YLB-04 scaffold23, whole genome shotgun sequenc...
Neobacillus piezotolerans strain YLB-04 scaffold23, whole genome shotgun sequence
gi|1444625838|ref|NZ_QNQT01000023.1 |WGS:NZ_QNQT01|scaffold23

Nucleotide
Homo sapiens mixed lineage kinase domain-like (MLKL), transcript variant 2, mRNA
Homo sapiens mixed lineage kinase domain-like (MLKL), transcript variant 2, mRNA
gi|215820621|ref|NM_001142497.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003922707	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Mar 31, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003922707

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Mar 31, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Three novel beta-hexosaminidase A mutations in obligate carriers of Tay-Sachs disease.

Tomczak J, Grebner EE.

Hum Mutat. 1994;4(1):71-2. No abstract available.

PubMed [citation]

PMID:: 7951261

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003922707.1

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

Description

Variant summary: HEXA c.1039_1056del18 (p.Asp347_Glu352del) results in an in-frame deletion that is predicted to remove six amino acids from the catalytic domain (IPR015883) of the encoded protein. The variant was absent in 251410 control chromosomes (gnomAD). c.1039_1056del18 has been reported in the literature in a Jewish female individual who was identified as a carrier through enzyme-based screening and who had a pregnancy that was determined prenatally to be affected with Tay-Sachs Disease (Tomczak_1994). To our knowledge, no experimental evidence directly examining the impact of the variant on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: May 13, 2023

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