NM_000521.4(HEXB):c.1614-14C>A AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Dec 10, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000079060.8

Allele description [Variation Report for NM_000521.4(HEXB):c.1614-14C>A]

NM_000521.4(HEXB):c.1614-14C>A

Gene:
HEXB:hexosaminidase subunit beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q13.3
Genomic location:
Preferred name:
NM_000521.4(HEXB):c.1614-14C>A
HGVS:
  • NC_000005.10:g.74721104C>A
  • NG_009770.2:g.86082C>A
  • NG_011531.1:g.51114G>T
  • NM_000521.4:c.1614-14C>AMANE SELECT
  • NM_001292004.1:c.939-14C>A
  • NC_000005.9:g.74016929C>A
  • NM_000521.3:c.1614-14C>A
Links:
dbSNP: rs201448394
NCBI 1000 Genomes Browser:
rs201448394
Molecular consequence:
  • NM_000521.4:c.1614-14C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001292004.1:c.939-14C>A - intron variant - [Sequence Ontology: SO:0001627]
Observations:
16

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000110929EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Benign
(Aug 29, 2012)
germlineclinical testing

Citation Link,

SCV000304649PreventionGenetics,PreventionGeneticscriteria provided, single submitter
Benigngermlineclinical testing

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

SCV000513237GeneDxcriteria provided, single submitter
Likely benign
(Feb 17, 2017)
germlineclinical testing

Citation Link,

SCV000919511Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Dec 10, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown16not providednot providednot providednot providedclinical testing
not providedgermlineyesnot 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

Characterization of seven novel mutations on the HEXB gene in French Sandhoff patients.

Gaignard P, Fagart J, Niemir N, Puech JP, Azouguene E, Dussau J, Caillaud C.

Gene. 2013 Jan 10;512(2):521-6. doi: 10.1016/j.gene.2012.09.124. Epub 2012 Oct 6.

PubMed [citation]
PMID:
23046579
See all PubMed Citations (3)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000110929.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided16not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided16not providednot providednot provided

From PreventionGenetics,PreventionGenetics, SCV000304649.1

#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 GeneDx, SCV000513237.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919511.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: HEXB c.1614-14C>A 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. 5/5 computational tools predict no significant impact on normal splicing, which a functional study, Sobek_2012, supports these predictions. The variant allele was found at a frequency of 0.00017 in 277098 control chromosomes (gnomAD and publication). This frequency is not significantly higher than expected for a pathogenic variant in HEXB causing Sandhoff Disease (0.00017 vs 0.0015), allowing no conclusion about variant significance. c.1614-14C>A has been reported in the literature in individuals affected with Sandhoff Disease (Giagnard_2013, Jarnes_2017, Sobek_2012). Although multiple reported affected individuals carried the variant in cis with another pathogenic HEXB variant, in particular, the exon 1-5 deletion, c.-117_669del was reported to be linked with the variant (Sobek_2012). Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Jul 10, 2021

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