NM_004380.3(CREBBP):c.6271A>T (p.Lys2091Ter) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 15, 2022
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:: RCV002864173.2

Allele description [Variation Report for NM_004380.3(CREBBP):c.6271A>T (p.Lys2091Ter)]

NM_004380.3(CREBBP):c.6271A>T (p.Lys2091Ter)

Gene:

CREBBP:CREB binding protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p13.3

Genomic location:

Preferred name:

NM_004380.3(CREBBP):c.6271A>T (p.Lys2091Ter)

HGVS:

NC_000016.10:g.3728776T>A
NG_009873.2:g.156938A>T
NM_001079846.1:c.6157A>T
NM_004380.3:c.6271A>TMANE SELECT
NP_001073315.1:p.Lys2053Ter
NP_004371.2:p.Lys2091Ter
LRG_1426t1:c.6271A>T
LRG_1426:g.156938A>T
LRG_1426p1:p.Lys2091Ter
NC_000016.9:g.3778777T>A
NM_004380.2:c.6271A>T

Protein change:

K2053*

Molecular consequence:

NM_001079846.1:c.6157A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004380.3:c.6271A>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003621837	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jun 15, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003621837

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jun 15, 2022)

germline

clinical testing

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

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

High prevalence of variants in skeletal dysplasia associated genes in individuals with short stature and minor skeletal anomalies.

Sentchordi-Montané L, Benito-Sanz S, Aza-Carmona M, Díaz-González F, Modamio-Høybjør S, de la Torre C, Nevado J, Ruiz-Ocaña P, Bezanilla-López C, Prieto P, Bahíllo-Curieses P, Carcavilla A, Mulero-Collantes I, Barreda-Bonis AC, Cruz-Rojo J, Ramírez-Fernández J, Bermúdez de la Vega JA, Travessa AM, González de Buitrago Amigo J, Del Pozo A, Vallespín E, Solís M, et al.

Eur J Endocrinol. 2021 Oct 11;185(5):691-705. doi: 10.1530/EJE-21-0557.

PubMed [citation]

PMID:: 34516402

Details of each submission

From Ambry Genetics, SCV003621837.2

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

Description

The c.6271A>T (p.K2091*) alteration, located in exon 31 (coding exon 31) of the CREBBP gene, consists of an A to T substitution at nucleotide position 6271. This changes the amino acid from a lysine (K) to a stop codon at amino acid position 2091. This alteration occurs at the 3' terminus of the CREBBP gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 14% of the protein. Premature stop codons are typically deleterious in nature, a significant portion of the protein is affected, and a downstream truncating alteration, p.Y2108*, has been reported as disease-causing (Sentchordi-Montané, 2021; Ambry internal data). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as 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: May 1, 2024

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