NM_001283009.1(RTEL1):c.3791G>A (p.Arg1264His) AND Dyskeratosis congenita, autosomal recessive 5

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Oct 23, 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:: RCV000034860.20

Allele description [Variation Report for NM_001283009.1(RTEL1):c.3791G>A (p.Arg1264His)]

NM_001283009.1(RTEL1):c.3791G>A (p.Arg1264His)

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_001283009.1(RTEL1):c.3791G>A (p.Arg1264His)

Other names:

uc021wge.1:c.3791G>A; NM_001283009.1:p.Arg1264His; p.Arg1010Ter

HGVS:

NC_000020.11:g.63695619G>A
NG_033901.1:g.42810G>A
NG_046961.1:g.3969G>A
NM_001283009.2:c.3791G>AMANE SELECT
NM_001283010.1:c.2983+139G>A
NM_016434.4:c.3652+139G>A
NM_032957.5:c.3724+139G>A
NP_001269938.1:p.Arg1264His
NP_001269938.1:p.Arg1264His
LRG_1149t1:c.3724+139G>A
LRG_1149t2:c.3791G>A
LRG_1149t3:c.3652+139G>A
LRG_1149:g.42810G>A
LRG_1149p2:p.Arg1264His
NC_000020.10:g.62326972G>A
NM_001283009.1:c.3791G>A
NM_001283009.2:c.3791G>A
NM_032957.4:c.3724+139G>A
NM_032957.5:c.3724+139G>A
NR_037882.1:n.4618G>A
p.Arg1264His

Protein change:

R1264H; ARG1264HIS

Links:

Counsyl: 143983; Genetic Testing Registry (GTR): GTR000575390; OMIM: 608833.0002; dbSNP: rs201540674

NCBI 1000 Genomes Browser:

rs201540674

Molecular consequence:

NM_001283010.1:c.2983+139G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_016434.4:c.3652+139G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_032957.5:c.3724+139G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001283009.2:c.3791G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_037882.1:n.4618G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000058464	OMIM	no assertion criteria provided	Pathogenic (Mar 15, 2015)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 23453664, 25607374
SCV000282030	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000485950	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Mar 3, 2016)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 24009516, 26025130, 25047097, 25620558, 25099625, 23453664 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf, Citation Link,
SCV004209330	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2023)	unknown	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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Ashkenazi Jewish	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Rare variants in RTEL1 are associated with familial interstitial pneumonia.

Cogan JD, Kropski JA, Zhao M, Mitchell DB, Rives L, Markin C, Garnett ET, Montgomery KH, Mason WR, McKean DF, Powers J, Murphy E, Olson LM, Choi L, Cheng DS, Blue EM, Young LR, Lancaster LH, Steele MP, Brown KK, Schwarz MI, Fingerlin TE, et al.

Am J Respir Crit Care Med. 2015 Mar 15;191(6):646-55. doi: 10.1164/rccm.201408-1510OC.

PubMed [citation]

PMID:: 25607374
PMCID:: PMC4384777

A recessive founder mutation in regulator of telomere elongation helicase 1, RTEL1, underlies severe immunodeficiency and features of Hoyeraal Hreidarsson syndrome.

Ballew BJ, Joseph V, De S, Sarek G, Vannier JB, Stracker T, Schrader KA, Small TN, O'Reilly R, Manschreck C, Harlan Fleischut MM, Zhang L, Sullivan J, Stratton K, Yeager M, Jacobs K, Giri N, Alter BP, Boland J, Burdett L, Offit K, Boulton SJ, et al.

PLoS Genet. 2013 Aug;9(8):e1003695. doi: 10.1371/journal.pgen.1003695. Epub 2013 Aug 29.

PubMed [citation]

PMID:: 24009516
PMCID:: PMC3757051

See all PubMed Citations (8)

Details of each submission

From OMIM, SCV000058464.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Dyskeratosis Congenita, Autosomal Recessive 5

For discussion of the arg1264-to-his (R1264H) mutation in the RTEL1 gene that was found in compound heterozygous state in a patient with autosomal recessive dyskeratosis congenita-5 (DKCB5; 615190) by Walne et al. (2013), see 608833.0001.

Pulmonary Fibrosis and/or Bone Marrow Failure Syndrome, Telomere-Related, 3

In affected members of a family (family E) with telomere-related pulmonary fibrosis without bone marrow failure (PFBMFT3; 616373), Cogan et al. (2015) identified a heterozygous c.3791G-A transition in the RTEL1 gene, resulting in an arg1264-to-his (R1264H) substitution in the 1,300-residue isoform.

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

From GeneReviews, SCV000282030.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Ashkenazi Jewish	not provided	not provided	not provided	literature only	PubMed (1)

#	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 Counsyl, SCV000485950.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

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

From Baylor Genetics, SCV004209330.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 7, 2024

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