NM_005732.4(RAD50):c.1174_1177del (p.Gln392fs) AND Nijmegen breakage syndrome-like disorder

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 23, 2019
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:: RCV000781782.5

Allele description [Variation Report for NM_005732.4(RAD50):c.1174_1177del (p.Gln392fs)]

NM_005732.4(RAD50):c.1174_1177del (p.Gln392fs)

Gene:

RAD50:RAD50 double strand break repair protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q31.1

Genomic location:

Preferred name:

NM_005732.4(RAD50):c.1174_1177del (p.Gln392fs)

HGVS:

NC_000005.10:g.132588809_132588812del
NG_021151.2:g.36833_36836del
NM_005732.4:c.1174_1177delMANE SELECT
NP_005723.2:p.Gln392fs
LRG_312t1:c.1174_1177del
LRG_312:g.36833_36836del
LRG_312p1:p.Gln392fs
NC_000005.9:g.131924498_131924501del
NC_000005.9:g.131924501_131924504del
NG_021151.1:g.36886_36889del
NM_005732.3:c.1174_1177del
NM_005732.3:c.1174_1177delCAGA

Protein change:

Q392fs

Links:

dbSNP: rs1554098250

NCBI 1000 Genomes Browser:

rs1554098250

Molecular consequence:

NM_005732.4:c.1174_1177del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Nijmegen breakage syndrome-like disorder (NBSLD)
Synonyms:: MICROCEPHALY AND SPONTANEOUS CHROMOSOME INSTABILITY WITHOUT IMMUNODEFICIENCY; NBS-LIKE DISORDER; RAD50 DEFICIENCY
Identifiers:: MONDO: MONDO:0013118; MedGen: C2751318; OMIM: 613078

Recent activity

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Homo sapiens HtrA serine peptidase 3 (HTRA3), transcript variant 1, mRNA
Homo sapiens HtrA serine peptidase 3 (HTRA3), transcript variant 1, mRNA
gi|1519314555|ref|NM_053044.5|

Nucleotide
TIGAR [Pongo abelii]
TIGAR [Pongo abelii]
Gene ID:100458705

Gene
LOC100555056 [Anolis carolinensis]
LOC100555056 [Anolis carolinensis]
Gene ID:100555056

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000920108	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jan 19, 2018)	germline	clinical testing	Citation Link,
SCV002019613	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 23, 2019)	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

SCV000920108

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jan 19, 2018)

germline

clinical testing

Citation Link,

SCV002019613

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 23, 2019)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000920108.1

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

Description

Variant summary: The RAD50 c.1174_1177delCAGA (p.Gln392LeufsX8) variant results in a premature termination codon, predicted to cause a truncated or absent RAD50 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 245944 control chromosomes. In addition, one clinical diagnostic laboratory/reputable database classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.

#	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

From Revvity Omics, Revvity, SCV002019613.3

#	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	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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