NM_003122.4(SPINK1):c.194+2T>C AND Hereditary pancreatitis

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 12, 2016
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:: RCV000119031.4

Allele description

NM_003122.4(SPINK1):c.194+2T>C

Gene:

SPINK1:serine peptidase inhibitor, Kazal type 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_003122.4(SPINK1):c.194+2T>C

Other names:

IVS3+2T>C

HGVS:

NC_000005.10:g.147828020A>G
NG_008356.2:g.16212T>C
NM_003122.4:c.194+2T>C
NC_000005.9:g.147207583A>G
NM_003122.3:c.194+2T>C

Links:

dbSNP: rs148954387

GMAF:

0.0008(G), 148954387

NCBI 1000 Genomes Browser:

rs148954387

Allele Frequency:

0.00036(G)

Molecular consequence:

NM_003122.4:c.194+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Hereditary pancreatitis (PCTT)
Synonyms:: PANCREATITIS, CHRONIC; Hereditary chronic pancreatitis; PRSS1-Related Hereditary Pancreatitis
Identifiers:: MedGen: C0238339; Orphanet: 676; OMIM: 167800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000153735	GeneReviews	no assertion criteria provided	Pathogenic (Mar 13, 2014)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000253884	Invitae,	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 12, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000153735

GeneReviews

no assertion criteria provided

Pathogenic
(Mar 13, 2014)

germline

literature only

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

SCV000253884

Invitae,

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 12, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

[-215G>A; IVS3+2T>C] mutation in the SPINK1 gene causes exon 3 skipping and loss of the trypsin binding site.

Kume K, Masamune A, Kikuta K, Shimosegawa T.

Gut. 2006 Aug;55(8):1214. No abstract available.

PubMed [citation]

PMID:: 16849362
PMCID:: PMC1856255

Details of each submission

From GeneReviews, SCV000153735.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

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

From Invitae,, SCV000253884.2

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

Description

This sequence change affects a donor splice site in intron 4 of the SPINK1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Loss-of-function variants in SPINK1 are known to be pathogenic. This particular variant is a common recurrent mutation found in ~20-45% of individuals of Asian decent with chronic pancreatitis (PMID: 23017645, 26632706, 15980664). Experimental studies have shown that this splice site variant completely abolishes expression of SPINK1 mRNA and protein in cell culture (PMID: 18978175). In summary, this is a well-known variant that is reported to abolish protein function and contribute to pancreatitis. For these reasons, this variant has been classified as Pathogenic.

#	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: Dec 9, 2017

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