NM_001283009.2(RTEL1):c.56A>G (p.Lys19Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 12, 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:: RCV001926337.3

Allele description [Variation Report for NM_001283009.2(RTEL1):c.56A>G (p.Lys19Arg)]

NM_001283009.2(RTEL1):c.56A>G (p.Lys19Arg)

Genes:

RTEL1-TNFRSF6B:RTEL1-TNFRSF6B readthrough (NMD candidate) [Gene - HGNC]
RTEL1:regulator of telomere elongation helicase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_001283009.2(RTEL1):c.56A>G (p.Lys19Arg)

HGVS:

NC_000020.11:g.63659458A>G
NG_033901.1:g.6649A>G
NM_001283009.2:c.56A>GMANE SELECT
NM_001283010.1:c.-568+999A>G
NM_016434.4:c.56A>G
NM_032957.5:c.56A>G
NP_001269938.1:p.Lys19Arg
NP_057518.1:p.Lys19Arg
NP_116575.3:p.Lys19Arg
LRG_1149t1:c.56A>G
LRG_1149t2:c.56A>G
LRG_1149t3:c.56A>G
LRG_1149:g.6649A>G
LRG_1149p1:p.Lys19Arg
LRG_1149p2:p.Lys19Arg
LRG_1149p3:p.Lys19Arg
NC_000020.10:g.62290811A>G
NR_037882.1:n.883A>G

Protein change:

K19R

Links:

dbSNP: rs2146141516

NCBI 1000 Genomes Browser:

rs2146141516

Molecular consequence:

NM_001283010.1:c.-568+999A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001283009.2:c.56A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_016434.4:c.56A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_032957.5:c.56A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_037882.1:n.883A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dyskeratosis congenita, autosomal recessive 5 (DKCB5)
Identifiers:: MONDO: MONDO:0014076; MedGen: C3554656; OMIM: 615190

Name:: Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 3
Synonyms:: PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE SYNDROME, TELOMERE-RELATED, 3
Identifiers:: MONDO: MONDO:0014613; MedGen: C4225346; Orphanet: 2032; OMIM: 616373

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002207312	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 12, 2021)	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

SCV002207312

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 12, 2021)

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 Invitae, SCV002207312.2

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

Description

This sequence change replaces lysine with arginine at codon 19 of the RTEL1 protein (p.Lys19Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RTEL1-related conditions. 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 arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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

Last Updated: Dec 24, 2023

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