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NM_006846.4(SPINK5):c.2113-2A>G AND Ichthyosis linearis circumflexa

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 4, 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:
RCV003762284.1

Allele description [Variation Report for NM_006846.4(SPINK5):c.2113-2A>G]

NM_006846.4(SPINK5):c.2113-2A>G

Gene:
SPINK5:serine peptidase inhibitor Kazal type 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q32
Genomic location:
Preferred name:
NM_006846.4(SPINK5):c.2113-2A>G
HGVS:
  • NC_000005.10:g.148118435A>G
  • NG_009633.1:g.59464A>G
  • NM_001127698.2:c.2113-2A>G
  • NM_001127699.2:c.2113-2A>G
  • NM_006846.4:c.2113-2A>GMANE SELECT
  • LRG_110:g.59464A>G
  • NC_000005.9:g.147497998A>G
Molecular consequence:
  • NM_001127698.2:c.2113-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001127699.2:c.2113-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_006846.4:c.2113-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Ichthyosis linearis circumflexa
Identifiers:
MONDO: MONDO:0043106; MedGen: C0265962

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004385276Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 4, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: implications for mutation detection and first case of prenatal diagnosis.

Sprecher E, Chavanas S, DiGiovanna JJ, Amin S, Nielsen K, Prendiville JS, Silverman R, Esterly NB, Spraker MK, Guelig E, de Luna ML, Williams ML, Buehler B, Siegfried EC, Van Maldergem L, Pfendner E, Bale SJ, Uitto J, Hovnanian A, Richard G.

J Invest Dermatol. 2001 Aug;117(2):179-87.

PubMed [citation]
PMID:
11511292
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004385276.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 22 of the SPINK5 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 SPINK5 are known to be pathogenic (PMID: 11511292, 11841556). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024