NM_181507.2(HPS5):c.2951+1G>A AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 19, 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:: RCV003687242.2

Allele description [Variation Report for NM_181507.2(HPS5):c.2951+1G>A]

NM_181507.2(HPS5):c.2951+1G>A

Gene:

HPS5:HPS5 biogenesis of lysosomal organelles complex 2 subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_181507.2(HPS5):c.2951+1G>A

HGVS:

NC_000011.10:g.18285345C>T
NG_008877.1:g.41830G>A
NM_007216.4:c.2609+1G>A
NM_181507.2:c.2951+1G>AMANE SELECT
NM_181508.1:c.2609+1G>A
LRG_586:g.41830G>A
NC_000011.9:g.18306892C>T

Molecular consequence:

NM_007216.4:c.2609+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181507.2:c.2951+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_181508.1:c.2609+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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BJ616505 NIBB Mochii normalized Xenopus early gastrula library Xenopus laevis cD...
BJ616505 NIBB Mochii normalized Xenopus early gastrula library Xenopus laevis cDNA clone XL177c18 5', mRNA sequence
gi|37252194|gnl|dbEST|19921516|dbj| 505.1|

Nucleotide
BJ622058 NIBB Mochii normalized Xenopus early gastrula library Xenopus laevis cD...
BJ622058 NIBB Mochii normalized Xenopus early gastrula library Xenopus laevis cDNA clone XL199k01 5', mRNA sequence
gi|37263354|gnl|dbEST|19927069|dbj| 058.1|

Nucleotide
Gene Links for GEO Profiles (Select 44331174) (1)
Gene
ANXA1 annexin A1 [Homo sapiens]
ANXA1 annexin A1 [Homo sapiens]
Gene ID:301

Gene
Chromosome neighbors for GEO Profiles (Select 44335050) (20)
GEO Profiles

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004432211	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 19, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 12548288, 15296495, 21833017, 26785811, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004432211

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 19, 2023)

germline

clinical testing

PubMed (6)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6.

Zhang Q, Zhao B, Li W, Oiso N, Novak EK, Rusiniak ME, Gautam R, Chintala S, O'Brien EP, Zhang Y, Roe BA, Elliott RW, Eicher EM, Liang P, Kratz C, Legius E, Spritz RA, O'Sullivan TN, Copeland NG, Jenkins NA, Swank RT.

Nat Genet. 2003 Feb;33(2):145-53. Epub 2003 Jan 27.

PubMed [citation]

PMID:: 12548288

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004432211.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with HPS5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 20 of the HPS5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HPS5 are known to be pathogenic (PMID: 12548288, 15296495, 21833017, 26785811).

#	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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