NM_133433.4(NIPBL):c.7168G>A (p.Ala2390Thr) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 11, 2017
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:: RCV002371984.2

Allele description [Variation Report for NM_133433.4(NIPBL):c.7168G>A (p.Ala2390Thr)]

NM_133433.4(NIPBL):c.7168G>A (p.Ala2390Thr)

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.7168G>A (p.Ala2390Thr)

HGVS:

NC_000005.10:g.37052471G>A
NG_006987.2:g.180589G>A
NM_015384.5:c.7168G>A
NM_133433.4:c.7168G>AMANE SELECT
NP_056199.2:p.Ala2390Thr
NP_597677.2:p.Ala2390Thr
NC_000005.9:g.37052573G>A
NG_006987.1:g.180589G>A
NM_133433.3:c.7168G>A
Q6KC79:p.Ala2390Thr

Protein change:

A2390T

Links:

UniProtKB: Q6KC79#VAR_021607; dbSNP: rs587784036

NCBI 1000 Genomes Browser:

rs587784036

Molecular consequence:

NM_015384.5:c.7168G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133433.4:c.7168G>A - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Uncertain function

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002662783	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Apr 11, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15318302, 23505322, 24038889 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002662783

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Apr 11, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations.

Gillis LA, McCallum J, Kaur M, DeScipio C, Yaeger D, Mariani A, Kline AD, Li HH, Devoto M, Jackson LG, Krantz ID.

Am J Hum Genet. 2004 Oct;75(4):610-23. Epub 2004 Aug 18.

PubMed [citation]

PMID:: 15318302
PMCID:: PMC1182048

High rate of mosaicism in individuals with Cornelia de Lange syndrome.

Huisman SA, Redeker EJ, Maas SM, Mannens MM, Hennekam RC.

J Med Genet. 2013 May;50(5):339-44. doi: 10.1136/jmedgenet-2012-101477. Epub 2013 Mar 15.

PubMed [citation]

PMID:: 23505322

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002662783.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.A2390T variant (also known as c.7168G>A), located in coding exon 41 of the NIPBL gene, results from a G to A substitution at nucleotide position 7168. The alanine at codon 2390 is replaced by threonine, an amino acid with similar properties. This variant was identified in 2 individuals with Cornelia de Lange syndrome. In one individual, this alteration occurred de novo, although paternity was not confirmed (Gillis LA et al. Am. J. Hum. Genet., 2004 Oct;75:610-23). The other individual was mosaic for this alteration; it was detected in buccal cells, but was absent in lymphocytes (Mannini L et al. Hum. Mutat., 2013 Dec;34:1589-96). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be 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

Last Updated: Sep 29, 2024

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