NM_003183.6(ADAM17):c.1846G>A (p.Asp616Asn) AND Inflammatory skin and bowel disease, neonatal, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2024
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:: RCV003051411.3

Allele description [Variation Report for NM_003183.6(ADAM17):c.1846G>A (p.Asp616Asn)]

NM_003183.6(ADAM17):c.1846G>A (p.Asp616Asn)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2p25.1

Genomic location:

Preferred name:

NM_003183.6(ADAM17):c.1846G>A (p.Asp616Asn)

HGVS:

NC_000002.12:g.9494705C>T
NG_029873.1:g.66084G>A
NM_001382777.1:c.1186G>A
NM_001382778.1:c.949G>A
NM_003183.6:c.1846G>AMANE SELECT
NP_001369706.1:p.Asp396Asn
NP_001369707.1:p.Asp317Asn
NP_003174.3:p.Asp616Asn
LRG_1203t1:c.1846G>A
LRG_1203:g.66084G>A
LRG_1203p1:p.Asp616Asn
NC_000002.11:g.9634834C>T

Protein change:

D317N

Molecular consequence:

NM_001382777.1:c.1186G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382778.1:c.949G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003183.6:c.1846G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003450105	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31060243, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003450105

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 2024)

germline

clinical testing

PubMed (2)
[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

Functional Characterization of Colon Cancer-Associated Mutations in ADAM17: Modifications in the Pro-Domain Interfere with Trafficking and Maturation.

Pavlenko E, Cabron AS, Arnold P, Dobert JP, Rose-John S, Zunke F.

Int J Mol Sci. 2019 May 4;20(9). doi: 10.3390/ijms20092198. Review.

PubMed [citation]

PMID:: 31060243
PMCID:: PMC6539446

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003450105.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 616 of the ADAM17 protein (p.Asp616Asn). This variant is present in population databases (rs756129840, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADAM17-related conditions. ClinVar contains an entry for this variant (Variation ID: 2143244). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects ADAM17 function (PMID: 31060243). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine