NM_133433.4(NIPBL):c.6455G>C (p.Arg2152Pro) AND Cornelia de Lange syndrome 1

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 22, 2020
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:: RCV001378278.7

Allele description [Variation Report for NM_133433.4(NIPBL):c.6455G>C (p.Arg2152Pro)]

NM_133433.4(NIPBL):c.6455G>C (p.Arg2152Pro)

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.6455G>C (p.Arg2152Pro)

HGVS:

NC_000005.10:g.37045554G>C
NG_006987.2:g.173672G>C
NM_015384.5:c.6455G>C
NM_133433.4:c.6455G>CMANE SELECT
NP_056199.2:p.Arg2152Pro
NP_597677.2:p.Arg2152Pro
NC_000005.9:g.37045656G>C

Protein change:

R2152P

Links:

dbSNP: rs781297222

NCBI 1000 Genomes Browser:

rs781297222

Molecular consequence:

NM_015384.5:c.6455G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133433.4:c.6455G>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001575815	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 22, 2020)	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

SCV001575815

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 22, 2020)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001575815.4

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with clinical features of Cornelia de Lange syndrome (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 2152 of the NIPBL protein (p.Arg2152Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline.

#	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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