NM_003183.6(ADAM17):c.2390del (p.Asp797fs) AND Inflammatory skin and bowel disease, neonatal, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 2, 2021
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:: RCV002221389.2

Allele description [Variation Report for NM_003183.6(ADAM17):c.2390del (p.Asp797fs)]

NM_003183.6(ADAM17):c.2390del (p.Asp797fs)

Genes:

ADAM17:ADAM metallopeptidase domain 17 [Gene - OMIM - HGNC]
IAH1:isoamyl acetate hydrolyzing esterase 1 (putative) [Gene - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p25.1

Genomic location:

Preferred name:

NM_003183.6(ADAM17):c.2390del (p.Asp797fs)

HGVS:

NC_000002.12:g.9490262del
NG_029873.1:g.70527del
NM_001382777.1:c.1730del
NM_001382778.1:c.1493del
NM_003183.6:c.2390delMANE SELECT
NP_001369706.1:p.Asp577fs
NP_001369707.1:p.Asp498fs
NP_003174.3:p.Asp797fs
LRG_1203t1:c.2390del
LRG_1203:g.70527del
LRG_1203p1:p.Asp797fs
NC_000002.11:g.9630391del
NM_003183.6:c.2390delAMANE SELECT

Protein change:

D498fs

Links:

dbSNP: rs2124947949

NCBI 1000 Genomes Browser:

rs2124947949

Molecular consequence:

NM_001382777.1:c.1730del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001382778.1:c.1493del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003183.6:c.2390del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Inflammatory skin and bowel disease, neonatal, 1
Identifiers:: MONDO: MONDO:0013693; MedGen: C3280501; Orphanet: 294023; OMIM: 614328

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002498620	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 2, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22010916, 25804906, 26683521, 29560122, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002498620

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 2, 2021)

germline

clinical testing

PubMed (5)
[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

Inflammatory skin and bowel disease linked to ADAM17 deletion.

Blaydon DC, Biancheri P, Di WL, Plagnol V, Cabral RM, Brooke MA, van Heel DA, Ruschendorf F, Toynbee M, Walne A, O'Toole EA, Martin JE, Lindley K, Vulliamy T, Abrams DJ, MacDonald TT, Harper JI, Kelsell DP.

N Engl J Med. 2011 Oct 20;365(16):1502-8. doi: 10.1056/NEJMoa1100721.

PubMed [citation]

PMID:: 22010916

Loss of ADAM17 is associated with severe multiorgan dysfunction.

Bandsma RH, van Goor H, Yourshaw M, Horlings RK, Jonkman MF, Schölvinck EH, Karrenbeld A, Scheenstra R, Kömhoff M, Rump P, Koopman-Keemink Y, Nelson SF, Escher JC, Cutz E, Martín MG.

Hum Pathol. 2015 Jun;46(6):923-8. doi: 10.1016/j.humpath.2015.02.010. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25804906
PMCID:: PMC6044207

See all PubMed Citations (5)

Details of each submission

From Molecular Genetics, Royal Melbourne Hospital, SCV002498620.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change is a deletion of 1 bp in exon 19 (of 19) of ADAM17 that is predicted to cause loss of the termination codon and elongate the protein by 28 amino acids creating a termination codon at position 853 (p.(Asp797Alafs*57)). Loss of function is the mechanism of disease for this gene (PMID: 22010916, 29560122, 26683521, 25804906). The variant is absent in a large population cohort (gnomAD v2.1 and v3.1), and has not been reported in the relevant medical literature of databases. Based on the classification scheme RMH Modified ACMG Guidelines v1.4.0, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PVS1_Moderate, PM2_Supporting.

#	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: Apr 15, 2024

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