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NM_004387.4(NKX2-5):c.847C>G (p.Pro283Ala) AND Atrial septal defect 7

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 3, 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:
RCV001915402.6

Allele description [Variation Report for NM_004387.4(NKX2-5):c.847C>G (p.Pro283Ala)]

NM_004387.4(NKX2-5):c.847C>G (p.Pro283Ala)

Gene:
NKX2-5:NK2 homeobox 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q35.1
Genomic location:
Preferred name:
NM_004387.4(NKX2-5):c.847C>G (p.Pro283Ala)
HGVS:
  • NC_000005.10:g.173232697G>C
  • NG_013340.1:g.7616C>G
  • NM_001166175.2:c.*800C>G
  • NM_001166176.2:c.*646C>G
  • NM_004387.4:c.847C>GMANE SELECT
  • NP_004378.1:p.Pro283Ala
  • LRG_671t1:c.847C>G
  • LRG_671:g.7616C>G
  • LRG_671p1:p.Pro283Ala
  • NC_000005.9:g.172659700G>C
Protein change:
P283A
Links:
dbSNP: rs2113900851
NCBI 1000 Genomes Browser:
rs2113900851
Molecular consequence:
  • NM_001166175.2:c.*800C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001166176.2:c.*646C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_004387.4:c.847C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Atrial septal defect 7
Synonyms:
Atrial septal defect with atrioventricular conduction defects; ASD WITH OR WITHOUT ATRIOVENTRICULAR CONDUCTION DEFECTS; Atrial septal defect 7 with or without atrioventricular conduction defects; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007173; MedGen: C3276096; Orphanet: 1479; OMIM: 108900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002167569Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 3, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV002167569.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NKX2-5-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 283 of the NKX2-5 protein (p.Pro283Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024