NM_000352.6(ABCC8):c.2017G>A (p.Asp673Asn) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 6, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003002828.4

Allele description [Variation Report for NM_000352.6(ABCC8):c.2017G>A (p.Asp673Asn)]

NM_000352.6(ABCC8):c.2017G>A (p.Asp673Asn)

Gene:

ABCC8:ATP binding cassette subfamily C member 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_000352.6(ABCC8):c.2017G>A (p.Asp673Asn)

HGVS:

NC_000011.10:g.17428312C>T
NG_008867.1:g.53591G>A
NM_000352.5:c.2017G>A
NM_000352.6:c.2017G>AMANE SELECT
NM_001287174.3:c.2017G>A
NM_001351295.2:c.2083G>A
NM_001351296.2:c.2014G>A
NM_001351297.2:c.2014G>A
NP_000343.2:p.Asp673Asn
NP_001274103.1:p.Asp673Asn
NP_001338224.1:p.Asp695Asn
NP_001338225.1:p.Asp672Asn
NP_001338226.1:p.Asp672Asn
LRG_790t1:c.2017G>A
LRG_790t2:c.2017G>A
LRG_790:g.53591G>A
LRG_790p1:p.Asp673Asn
LRG_790p2:p.Asp673Asn
NC_000011.9:g.17449859C>T
NR_147094.2:n.2083G>A

Protein change:

D672N

Molecular consequence:

NM_000352.6:c.2017G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001287174.3:c.2017G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351295.2:c.2083G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351296.2:c.2014G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001351297.2:c.2014G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_147094.2:n.2083G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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LOC4344380 [Oryza sativa Japonica Group]
LOC4344380 [Oryza sativa Japonica Group]
Gene ID:4344380

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003299800	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31595705, 28492532
SCV004238852	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 6, 2023)	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

SCV003299800

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004238852

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 6, 2023)

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

Targeted sequencing identifies novel variants in common and rare MODY genes.

de Santana LS, Caetano LA, Costa-Riquetto AD, Franco PC, Dotto RP, Reis AF, Weinert LS, Silveiro SP, Vendramini MF, do Prado FA, Abrahão GCP, de Almeida AGFP, Tavares MDGR, Gonçalves WRB, Santomauro Junior AC, Halpern B, Jorge AAL, Nery M, Teles MG.

Mol Genet Genomic Med. 2019 Dec;7(12):e962. doi: 10.1002/mgg3.962. Epub 2019 Oct 8.

PubMed [citation]

PMID:: 31595705
PMCID:: PMC6900361

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003299800.1

#	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 with asparagine at codon 673 of the ABCC8 protein (p.Asp673Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs777986828, ExAC 0.003%). This missense change has been observed in individual(s) with ABCC8-related conditions (PMID: 31595705). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ABCC8 protein function. 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

From Revvity Omics, Revvity, SCV004238852.1

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

#	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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