NM_003183.6(ADAM17):c.2452G>C (p.Asp818His) AND Inflammatory skin and bowel disease, neonatal, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 24, 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:: RCV001938372.6

Allele description [Variation Report for NM_003183.6(ADAM17):c.2452G>C (p.Asp818His)]

NM_003183.6(ADAM17):c.2452G>C (p.Asp818His)

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.2452G>C (p.Asp818His)

HGVS:

NC_000002.12:g.9490200C>G
NG_029873.1:g.70589G>C
NM_001382777.1:c.1792G>C
NM_001382778.1:c.1555G>C
NM_003183.6:c.2452G>CMANE SELECT
NP_001369706.1:p.Asp598His
NP_001369707.1:p.Asp519His
NP_003174.3:p.Asp818His
LRG_1203t1:c.2452G>C
LRG_1203:g.70589G>C
LRG_1203p1:p.Asp818His
NC_000002.11:g.9630329C>G

Protein change:

D519H

Links:

dbSNP: rs142315365

NCBI 1000 Genomes Browser:

rs142315365

Molecular consequence:

NM_001382777.1:c.1792G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001382778.1:c.1555G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003183.6:c.2452G>C - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002197017	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 24, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002197017

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 24, 2022)

germline

clinical testing

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

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

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, SCV002197017.3

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with ADAM17-related conditions. This variant is present in population databases (rs142315365, gnomAD 0.02%). This sequence change replaces aspartic acid with histidine at codon 818 of the ADAM17 protein (p.Asp818His). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and histidine.

#	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

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