NM_000263.4(NAGLU):c.2183AGA[1] (p.Lys729del) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 27, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV003133495.4

Allele description [Variation Report for NM_000263.4(NAGLU):c.2183AGA[1] (p.Lys729del)]

NM_000263.4(NAGLU):c.2183AGA[1] (p.Lys729del)

Gene:

NAGLU:N-acetyl-alpha-glucosaminidase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_000263.4(NAGLU):c.2183AGA[1] (p.Lys729del)

HGVS:

NC_000017.11:g.42544189AGA[1]
NG_011552.1:g.13257AGA[1]
NM_000263.3:c.2186_2188del
NM_000263.4:c.2183AGA[1]MANE SELECT
NP_000254.2:p.Lys729del
NC_000017.10:g.40696206_40696208del
NC_000017.10:g.40696207AGA[1]
NM_000263.3:c.2186_2188delAGA

Protein change:

K729del

Links:

dbSNP: rs1216052074

NCBI 1000 Genomes Browser:

rs1216052074

Molecular consequence:

NM_000263.4:c.2183AGA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003813417	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 15, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005333670	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 27, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003813417

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 15, 2020)

germline

clinical testing

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

SCV005333670

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 27, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Details of each submission

From Revvity Omics, Revvity, SCV003813417.2

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

#	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

From GeneDx, SCV005333670.1

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

Description

Published functional studies found this variant is associated with significantly reduced enzyme activity (PMID: 11153910); In-frame deletion of one amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Also known as c.2185delAGA; This variant is associated with the following publications: (PMID: 34806811, 22976768, 11153910)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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