NM_003839.4(TNFRSF11A):c.18_30del (p.Arg7fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 17, 2023
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:: RCV003672599.2

Allele description [Variation Report for NM_003839.4(TNFRSF11A):c.18_30del (p.Arg7fs)]

NM_003839.4(TNFRSF11A):c.18_30del (p.Arg7fs)

Genes:

LOC130062628:ATAC-STARR-seq lymphoblastoid silent region 9505 [Gene]
TNFRSF11A:TNF receptor superfamily member 11a [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

18q21.33

Genomic location:

Preferred name:

NM_003839.4(TNFRSF11A):c.18_30del (p.Arg7fs)

HGVS:

NC_000018.10:g.62325370_62325382del
NG_008098.1:g.5056_5068del
NG_195520.1:g.269_281del
NM_001270949.2:c.18_30del
NM_001270950.2:c.18_30del
NM_001270951.2:c.18_30del
NM_001278268.2:c.18_30del
NM_003839.4:c.18_30delMANE SELECT
NP_001257878.1:p.Arg7fs
NP_001257879.1:p.Arg7fs
NP_001257880.1:p.Arg7fs
NP_001265197.1:p.Arg7fs
NP_003830.1:p.Arg7Cysfs
NP_003830.1:p.Arg7fs
LRG_194t1:c.18_30del
LRG_194:g.5056_5068del
LRG_194p1:p.Arg7Cysfs
NC_000018.9:g.59992597_59992609del
NC_000018.9:g.59992603_59992615del
NM_003839.2:c.18_30delGCGGCGCCGCCCG

Protein change:

R7fs

Molecular consequence:

NM_001270949.2:c.18_30del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270950.2:c.18_30del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001270951.2:c.18_30del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001278268.2:c.18_30del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003839.4:c.18_30del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV004390102	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10677500, 18606301, 22271396, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004390102

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 17, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism.

Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan SC, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, et al.

Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1566-71.

PubMed [citation]

PMID:: 10677500
PMCID:: PMC26475

Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to TNFRSF11A (RANK) mutations.

Guerrini MM, Sobacchi C, Cassani B, Abinun M, Kilic SS, Pangrazio A, Moratto D, Mazzolari E, Clayton-Smith J, Orchard P, Coxon FP, Helfrich MH, Crockett JC, Mellis D, Vellodi A, Tezcan I, Notarangelo LD, Rogers MJ, Vezzoni P, Villa A, Frattini A.

Am J Hum Genet. 2008 Jul;83(1):64-76. doi: 10.1016/j.ajhg.2008.06.015.

PubMed [citation]

PMID:: 18606301
PMCID:: PMC2443850

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004390102.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with TNFRSF11A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg7Cysfs*172) in the TNFRSF11A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TNFRSF11A are known to be pathogenic (PMID: 10677500, 18606301, 22271396).

#	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: Sep 29, 2024

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