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Andrea Oza

Andrea Oza

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Disease

Chronic pancreatitis

Inheritance

Autosomal dominant

Prevalence

Expand
titlePossible sources

Orphanet

Medline Plus Genetics

 

Source:

Rapid or full curation?

  •  Rapid
  •  Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

ClinGen - dosage sensitivitiy, sufficient evidence for haploinsufficiency. GenCC - only US lab is Invitae (strong). No BabySeq.

Clinical Validity Scoring Notes and points

From Dosage sensitivity:

  • PUBMED: 17681820 - Masson et al. (2007) identified a 30,588-bp deletion encompassing the entire SPINK1 gene in a 47 year old female with chronic pancreatitis and her affected father and paternal uncle. 2 point LOF

  • PUBMED: 22427236 - Rosendahl et al. (2013) used PCR and gene sequencing on 660 unrelated individuals with hereditary chronic pancreatitis (HP) or Idiopathic chronic pancreatitis (ICP) and a control group of 1758 individuals. 12 variants were detected in SPINK1, 10 variants were missense, a variant found in one individual was frameshift (p.V60YfsX35), and a variant found in one individual was a deletion (c.27delC). Inheritance for all variants identified is unknown. 2x2 point LOF = 4 points

  • PUBMED: 16823394 Previously, a heterozygous 1,336-bp deletion encompassing exon 1 of the SPINK1 gene was detected in an individual and her two brothers, both with chronic pancreatitis, by HPLC. Parental samples were unavailable. 2 point

  • PUBMED: 14722925 Marechal, et al. (2003) used denaturing high performance liquid chromatography (DHPLC) and PCR on 46 families with pancreatitis. Two families were identified to have a microdeletion in SPINK1 (c.27delC). In Family 1, three individuals were identified to have this variant, two affected family members and one unaffected family member. In Family 2, 7 individuals had this variant, 2 affected and 5 unaffected. Confirmed these are different authors from PMID: 22427236. 2x2 point = 4 point.

Source:

Clinical Validity Points Total

12

Source:

Clinical Validity Classification

Expand
titleClassifications (pts)

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Definitive

Source:

Molecular Mechanism

Expand
titleMechanisms

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function

Penetrance

Expand
titleoptions

Complete (100%)

High (≥80%)

Moderate  (<80% and >20%)

Low (≤20%)

(list source/PMID)

Source:

Age of Onset

Expand
titleoptions

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

Severity

Expand
titleOptions

Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.

Clinical Features

Sources:

HPO Terms

https://hpo.jax.org/app/

Gene SOPs & Notes

 LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant

Curation Summary

Expand
titleExamples

- The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited

The SPINK1 gene is associated with autosomal dominant chronic pancreatitis, which is is characterized by inflammation of the pancreas. Symptoms can include abdominal pain, steatorrhea, abdominal symptoms (bloating, gas, cramps, diarrhea), elevated serum amylase or lipase, systemic inflammation, and multiorgan failure (PMID: 24624459). Risk factors for chronic pancreatitis include smoking, alcohol use, and genetic risk.

Case ID, Curator name, Date, Jira ticket link

AO 01.24.25 56752207081045