NM_000308.4(CTSA):c.275_278del (p.Asp92fs) AND Combined deficiency of sialidase AND beta galactosidase

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 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:: RCV003495093.2

Allele description [Variation Report for NM_000308.4(CTSA):c.275_278del (p.Asp92fs)]

NM_000308.4(CTSA):c.275_278del (p.Asp92fs)

Gene:

CTSA:cathepsin A [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_000308.4(CTSA):c.275_278del (p.Asp92fs)

HGVS:

NC_000020.11:g.45891996_45891999del
NG_008291.1:g.6045_6048del
NG_033108.1:g.4290_4293del
NM_000308.4:c.275_278delMANE SELECT
NM_001127695.3:c.275_278del
NM_001167594.3:c.275_278del
NP_000299.3:p.Asp92fs
NP_001121167.1:p.Asp92fs
NP_001161066.2:p.Asp92fs
NC_000020.10:g.44520634_44520637del
NC_000020.10:g.44520635_44520638del
NR_133656.2:n.320_323del

Protein change:

D92fs

Molecular consequence:

NM_000308.4:c.275_278del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127695.3:c.275_278del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167594.3:c.275_278del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_133656.2:n.320_323del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Combined deficiency of sialidase AND beta galactosidase (GSL)
Synonyms:: CATHEPSIN A DEFICIENCY; Galactosialidosis; Goldberg syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009737; MedGen: C0268233; Orphanet: 351; OMIM: 256540

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004308292	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 26, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15110321, 23915561, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004308292

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 26, 2023)

germline

clinical testing

PubMed (3)
[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

Citations

PubMed

New mutations in the PPBG gene lead to loss of PPCA protein which affects the level of the beta-galactosidase/neuraminidase complex and the EBP-receptor.

Malvagia S, Morrone A, Caciotti A, Bardelli T, d'Azzo A, Ancora G, Zammarchi E, Donati MA.

Mol Genet Metab. 2004 May;82(1):48-55.

PubMed [citation]

PMID:: 15110321

Galactosialidosis: review and analysis of CTSA gene mutations.

Caciotti A, Catarzi S, Tonin R, Lugli L, Perez CR, Michelakakis H, Mavridou I, Donati MA, Guerrini R, d'Azzo A, Morrone A.

Orphanet J Rare Dis. 2013 Aug 2;8:114. doi: 10.1186/1750-1172-8-114. Review.

PubMed [citation]

PMID:: 23915561
PMCID:: PMC3737020

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004308292.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Asp110Glyfs*27) in the CTSA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTSA are known to be pathogenic (PMID: 15110321, 23915561). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CTSA-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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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