NM_024312.5(GNPTAB):c.2693del (p.Lys898fs) AND multiple conditions

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000673774.5

Allele description [Variation Report for NM_024312.5(GNPTAB):c.2693del (p.Lys898fs)]

NM_024312.5(GNPTAB):c.2693del (p.Lys898fs)

Gene:

GNPTAB:N-acetylglucosamine-1-phosphate transferase subunits alpha and beta [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_024312.5(GNPTAB):c.2693del (p.Lys898fs)

HGVS:

NC_000012.12:g.101764231del
NG_021243.1:g.71644del
NM_024312.5:c.2693delMANE SELECT
NP_077288.2:p.Lys898fs
NC_000012.11:g.102158002del
NC_000012.11:g.102158009del
NM_024312.4:c.2693delA
NM_024312.5:c.2693delAMANE SELECT

Protein change:

K898fs

Links:

dbSNP: rs281864999

NCBI 1000 Genomes Browser:

rs281864999

Molecular consequence:

NM_024312.5:c.2693del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Mucolipidosis type II
Synonyms:: ML II ALPHA/BETA; I cell disease; Mucolipidosis 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009650; MedGen: C2673377; Orphanet: 576; OMIM: 252500

Name:: Pseudo-Hurler polydystrophy (ML3)
Synonyms:: ML III; ML III ALPHA/BETA; Mucolipidosis type 3A; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018931; MedGen: C0033788; Orphanet: 577; OMIM: 252600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000799017	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Apr 4, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002219883	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 21, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19197337, 19617216, 25107912, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000799017

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Apr 4, 2018)

unknown

clinical testing

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

Citation Link,

SCV002219883

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 21, 2023)

germline

clinical testing

PubMed (4)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mucolipidosis II and III alpha/beta: mutation analysis of 40 Japanese patients showed genotype-phenotype correlation.

Otomo T, Muramatsu T, Yorifuji T, Okuyama T, Nakabayashi H, Fukao T, Ohura T, Yoshino M, Tanaka A, Okamoto N, Inui K, Ozono K, Sakai N.

J Hum Genet. 2009 Mar;54(3):145-51. doi: 10.1038/jhg.2009.3. Epub 2009 Feb 6.

PubMed [citation]

PMID:: 19197337

Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands.

Cathey SS, Leroy JG, Wood T, Eaves K, Simensen RJ, Kudo M, Stevenson RE, Friez MJ.

J Med Genet. 2010 Jan;47(1):38-48. doi: 10.1136/jmg.2009.067736. Epub 2009 Jul 16.

PubMed [citation]

PMID:: 19617216
PMCID:: PMC3712854

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000799017.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002219883.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 39058). This premature translational stop signal has been observed in individual(s) with mucolipidosis III (PMID: 19197337). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Lys898Serfs*13) in the GNPTAB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNPTAB are known to be pathogenic (PMID: 19617216, 25107912).

#	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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