NM_020944.3(GBA2):c.2506-2A>G AND Hereditary spastic paraplegia 46

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 28, 2022
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:: RCV002465072.3

Allele description [Variation Report for NM_020944.3(GBA2):c.2506-2A>G]

NM_020944.3(GBA2):c.2506-2A>G

Gene:

GBA2:glucosylceramidase beta 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_020944.3(GBA2):c.2506-2A>G

HGVS:

NC_000009.12:g.35737449T>C
NG_033899.1:g.16780A>G
NG_046983.1:g.10130T>C
NM_001330660.2:c.*27A>G
NM_020944.3:c.2506-2A>GMANE SELECT
NC_000009.11:g.35737446T>C

Molecular consequence:

NM_001330660.2:c.*27A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_020944.3:c.2506-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Name:: Hereditary spastic paraplegia 46
Synonyms:: Spastic paraplegia 46, autosomal recessive
Identifiers:: MONDO: MONDO:0013737; MedGen: C2828721; Orphanet: 320391; OMIM: 614409

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002759467	Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 28, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002759467

Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 28, 2022)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	1	1	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 Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology, SCV002759467.1

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

Description

The c.2506-2A>G is not present in publicly available population databases like 1000 Genomes, EVS, ExAC, gnomAD, Indian Exome Database or our in-house exome database. The variant has neither been published in literature nor reported to clinical databases like ClinVar, Human Genome Mutation Database (HGMD) and/or OMIM, in any affected individuals. In silico pathogenicity programs like MutationTaster2, CADD, Varsome, HSF3.1 etc. predicted this variant to be likely deleterious by causing splicing aberration, however these predictions were not confirmed by any published functional/translational studies.

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

Last Updated: Jun 24, 2023

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