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NM_002907.4(RECQL):c.1465A>G (p.Ile489Val) AND not provided

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Oct 23, 2024
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:
RCV001206987.15

Allele description [Variation Report for NM_002907.4(RECQL):c.1465A>G (p.Ile489Val)]

NM_002907.4(RECQL):c.1465A>G (p.Ile489Val)

Gene:
RECQL:RecQ like helicase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p12.1
Genomic location:
Preferred name:
NM_002907.4(RECQL):c.1465A>G (p.Ile489Val)
HGVS:
  • NC_000012.12:g.21471630T>C
  • NG_053196.1:g.39027T>C
  • NM_002907.4:c.1465A>GMANE SELECT
  • NM_032941.3:c.1465A>G
  • NP_002898.2:p.Ile489Val
  • NP_116559.1:p.Ile489Val
  • NC_000012.11:g.21624564T>C
  • NM_002907.3:c.1465A>G
Protein change:
I489V
Links:
dbSNP: rs146077019
NCBI 1000 Genomes Browser:
rs146077019
Molecular consequence:
  • NM_002907.4:c.1465A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032941.3:c.1465A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001378322Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 27, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001785780GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Uncertain significance
(Aug 8, 2024)
germlineclinical testing

Citation Link,

SCV002046714Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Uncertain significance
(Oct 23, 2024)
unknownclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot 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

The genetics of hereditary cancer risk syndromes in Brazil: a comprehensive analysis of 1682 patients.

de Oliveira JM, Zurro NB, Coelho AVC, Caraciolo MP, de Alexandre RB, Cervato MC, Minillo RM, de Vasconcelos Carvalho Neto G, Grivicich I, Oliveira JB.

Eur J Hum Genet. 2022 Jul;30(7):818-823. doi: 10.1038/s41431-022-01098-7. Epub 2022 May 9.

PubMed [citation]
PMID:
35534704
PMCID:
PMC9259741
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001378322.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 489 of the RECQL protein (p.Ile489Val). This variant is present in population databases (rs146077019, gnomAD 0.05%). This missense change has been observed in individual(s) with breast cancer and/or pancreatic cancer (PMID: 19768149, 35264596). ClinVar contains an entry for this variant (Variation ID: 584806). 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 RECQL protein function with a negative predictive value of 80%. 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.

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

From GeneDx, SCV001785780.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Observed in individuals with breast cancer, leukemia, or pancreatic cancer (PMID: 19768149, 35264596, 35534704); In silico analysis indicates that this missense variant does not alter protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868); This variant is associated with the following publications: (PMID: 35264596, 19768149, 35534704, 27248010, 19151156, 23396353)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002046714.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

The RECQL c.1465A>G (p.Ile489Val) variant has been reported in the published literature in individuals with stomach cancer (PMID: 35534704 (2022)), pancreatic cancer (PMID: 19768149 (2009)), breast cancer (PMID: 35264596 (2022), 33471991 (2021) see also LOVD (http://databases.lovd.nl/shared/)), and reportedly healthy individuals (PMID: 33471991 (2021) see also LOVD (http://databases.lovd.nl/shared/)). The frequency of this variant in the general population, 0.00046 (14/30580 chromosomes in South Asian subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

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

Last Updated: Feb 1, 2025