NM_000520.6(HEXA):c.1527-6T>C AND not specified

Clinical significance:Likely benign (Last evaluated: Aug 7, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000246203.4

Allele description [Variation Report for NM_000520.6(HEXA):c.1527-6T>C]

NM_000520.6(HEXA):c.1527-6T>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.1527-6T>C
HGVS:
  • NC_000015.10:g.72344146A>G
  • NG_009017.1:g.37034T>C
  • NG_009017.2:g.37034T>C
  • NM_000520.6:c.1527-6T>CMANE SELECT
  • NM_001318825.2:c.1560-6T>C
  • NC_000015.9:g.72636487A>G
  • NM_000520.4:c.1527-6T>C
  • NM_000520.5:c.1527-6T>C
Links:
dbSNP: rs199914308
NCBI 1000 Genomes Browser:
rs199914308
Molecular consequence:
  • NM_000520.6:c.1527-6T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001318825.2:c.1560-6T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000304641PreventionGenetics,PreventionGeneticscriteria provided, single submitter
Likely benigngermlineclinical testing

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

SCV001431934Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Aug 7, 2020)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene.

Myerowitz R.

Hum Mutat. 1997;9(3):195-208. Review.

PubMed [citation]
PMID:
9090523

Details of each submission

From PreventionGenetics,PreventionGenetics, SCV000304641.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001431934.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: HEXA c.1527-6T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0012 in 251334 control chromosomes, predominantly at a frequency of 0.0013 within the Latino subpopulation in the gnomAD database. This frequency is slightly lower than expected for a pathogenic variant in HEXA causing Tay-Sachs Disease (0.0012 vs 0.0014), suggesting this variant may be benign. c.1527-6T>C has been reported in the literature in individuals affected with Tay-Sachs Disease and classified as neutral polymorphism (Myerowitz_1997). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (Likely benign n=2, VUS n=2). Based on the evidence outlined above, the variant was classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2021

Support Center