NM_002907.4(RECQL):c.1795A>G (p.Arg599Gly) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 25, 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:: RCV001763111.7

Allele description [Variation Report for NM_002907.4(RECQL):c.1795A>G (p.Arg599Gly)]

NM_002907.4(RECQL):c.1795A>G (p.Arg599Gly)

Genes:

RECQL:RecQ like helicase [Gene - OMIM - HGNC]
PYROXD1:pyridine nucleotide-disulphide oxidoreductase domain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p12.1

Genomic location:

Preferred name:

NM_002907.4(RECQL):c.1795A>G (p.Arg599Gly)

HGVS:

NC_000012.12:g.21470971T>C
NG_053196.1:g.38368T>C
NM_001350912.2:c.*2217T>C
NM_001350913.2:c.*2217T>C
NM_002907.4:c.1795A>GMANE SELECT
NM_024854.5:c.*2217T>CMANE SELECT
NM_032941.3:c.1795A>G
NP_002898.2:p.Arg599Gly
NP_116559.1:p.Arg599Gly
NC_000012.11:g.21623905T>C
NM_002907.3:c.1795A>G

Protein change:

R599G

Links:

dbSNP: rs773438480

NCBI 1000 Genomes Browser:

rs773438480

Molecular consequence:

NM_001350912.2:c.*2217T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001350913.2:c.*2217T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_024854.5:c.*2217T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_002907.4:c.1795A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_032941.3:c.1795A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001991681	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 2, 2019)	germline	clinical testing	Citation Link,
SCV002207222	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 25, 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

SCV001991681

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 2, 2019)

germline

clinical testing

Citation Link,

SCV002207222

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 25, 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
not provided	germline	yes	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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV001991681.2

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002207222.3

#	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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1307575). This variant has not been reported in the literature in individuals affected with RECQL-related conditions. This variant is present in population databases (rs773438480, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 599 of the RECQL protein (p.Arg599Gly).

#	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: Jun 2, 2024

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