NM_133433.4(NIPBL):c.2294G>A (p.Arg765Lys) AND Cornelia de Lange syndrome 1

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(2);Uncertain significance(1) (Last evaluated: Dec 31, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000146540.4

Allele description [Variation Report for NM_133433.4(NIPBL):c.2294G>A (p.Arg765Lys)]

NM_133433.4(NIPBL):c.2294G>A (p.Arg765Lys)

Gene:
NIPBL:NIPBL cohesin loading factor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5p13.2
Genomic location:
Preferred name:
NM_133433.4(NIPBL):c.2294G>A (p.Arg765Lys)
HGVS:
  • NC_000005.10:g.36985474G>A
  • NG_006987.1:g.113592G>A
  • NG_006987.2:g.113592G>A
  • NM_015384.5:c.2294G>A
  • NM_133433.4:c.2294G>AMANE SELECT
  • NP_056199.2:p.Arg765Lys
  • NP_597677.2:p.Arg765Lys
  • NC_000005.9:g.36985576G>A
  • NM_133433.3:c.2294G>A
Protein change:
R765K
Links:
dbSNP: rs185678374
NCBI 1000 Genomes Browser:
rs185678374
Molecular consequence:
  • NM_015384.5:c.2294G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133433.4:c.2294G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cornelia de Lange syndrome 1 (CDLS1)
Synonyms:
Typus degenerativus amstelodamensis; Brachmann de Lange syndrome
Identifiers:
MONDO: MONDO:0007387; MedGen: C4551851; Orphanet: 199; OMIM: 122470

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000193835Genetic Services Laboratory,University of Chicagocriteria provided, single submitter
Uncertain significance
(Feb 8, 2013)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000457277Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Likely benign
(Jan 13, 2018)
germlineclinical testing

Citation Link,

SCV001016592Invitaecriteria provided, single submitter
Likely benign
(Dec 31, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]
PMID:
18414213

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 Genetic Services Laboratory,University of Chicago, SCV000193835.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV000457277.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001016592.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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