NM_006846.4(SPINK5):c.2870del (p.Leu957fs) AND Ichthyosis linearis circumflexa

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 23, 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:: RCV003763554.1

Allele description [Variation Report for NM_006846.4(SPINK5):c.2870del (p.Leu957fs)]

NM_006846.4(SPINK5):c.2870del (p.Leu957fs)

Gene:

SPINK5:serine peptidase inhibitor Kazal type 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_006846.4(SPINK5):c.2870del (p.Leu957fs)

HGVS:

NC_000005.10:g.148126985del
NG_009633.1:g.68014del
NM_001127698.2:c.2960del
NM_006846.4:c.2870delMANE SELECT
NP_001121170.1:p.Leu987fs
NP_006837.2:p.Leu957Glnfs
NP_006837.2:p.Leu957fs
LRG_110t1:c.2870del
LRG_110:g.68014del
LRG_110p1:p.Leu957Glnfs
NC_000005.9:g.147506548del
NM_006846.3:c.2870delT

Protein change:

L957fs

Molecular consequence:

NM_001127698.2:c.2960del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_006846.4:c.2870del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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SUGT1P3 SUGT1 pseudogene 3 [Homo sapiens]
SUGT1P3 SUGT1 pseudogene 3 [Homo sapiens]
Gene ID:283507

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004507443	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 23, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11511292, 11841556, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004507443

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 23, 2022)

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

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

Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families.

Bitoun E, Chavanas S, Irvine AD, Lonie L, Bodemer C, Paradisi M, Hamel-Teillac D, Ansai S, Mitsuhashi Y, Taïeb A, de Prost Y, Zambruno G, Harper JI, Hovnanian A.

J Invest Dermatol. 2002 Feb;118(2):352-61.

PubMed [citation]

PMID:: 11841556

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004507443.1

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. This variant is present in population databases (rs766754092, gnomAD 0.03%). This sequence change creates a premature translational stop signal (p.Leu957Glnfs*46) in the SPINK5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPINK5 are known to be pathogenic (PMID: 11511292, 11841556).

#	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: Feb 28, 2024

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