NM_057175.5(NAA15):c.239_240del (p.His80fs) AND Intellectual disability, autosomal dominant 50

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Apr 11, 2023
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:: RCV000677626.11

Allele description

NM_057175.5(NAA15):c.239_240del (p.His80fs)

Gene:

NAA15:N-alpha-acetyltransferase 15, NatA auxiliary subunit [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

4q31.1

Genomic location:

Preferred name:

NM_057175.5(NAA15):c.239_240del (p.His80fs)

HGVS:

NC_000004.12:g.139336947_139336948del
NG_053037.1:g.40481_40482del
NM_057175.5:c.239_240delMANE SELECT
NP_476516.1:p.His80fs
NC_000004.11:g.140258101_140258102del
NM_057175.3:c.239_240del
NM_057175.3:c.239_240delAT
NM_057175.4:c.239_240del
NM_057175.4:c.239_240delAT
NM_057175.5:c.239_240delATMANE SELECT

Protein change:

H80fs

Links:

OMIM: 608000.0004; dbSNP: rs779009256

NCBI 1000 Genomes Browser:

rs779009256

Molecular consequence:

NM_057175.5:c.239_240del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Intellectual disability, autosomal dominant 50
Synonyms:: MENTAL RETARDATION, AUTOSOMAL DOMINANT 50; INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 50, WITH BEHAVIORAL ABNORMALITIES
Identifiers:: MONDO: MONDO:0030916; MedGen: C4540470; OMIM: 617787

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000803755	OMIM	no assertion criteria provided	Pathogenic (Jul 7, 2021)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 29656860, 28191889
SCV001528440	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 5, 2018)	maternal	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28303347, 25741868
SCV002559202	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002583438	Clinical Genetics Laboratory, University Hospital Schleswig-Holstein	no assertion criteria provided	Pathogenic (Apr 5, 2022)	germline	clinical testing
SCV002779055	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 30, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003915704	Daryl Scott Lab, Baylor College of Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 11, 2023)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.

Cheng H, Dharmadhikari AV, Varland S, Ma N, Domingo D, Kleyner R, Rope AF, Yoon M, Stray-Pedersen A, Posey JE, Crews SR, Eldomery MK, Akdemir ZC, Lewis AM, Sutton VR, Rosenfeld JA, Conboy E, Agre K, Xia F, Walkiewicz M, Longoni M, High FA, et al.

Am J Hum Genet. 2018 May 3;102(5):985-994. doi: 10.1016/j.ajhg.2018.03.004. Epub 2018 Apr 12.

PubMed [citation]

PMID:: 29656860
PMCID:: PMC5986698

Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.

Stessman HA, Xiong B, Coe BP, Wang T, Hoekzema K, Fenckova M, Kvarnung M, Gerdts J, Trinh S, Cosemans N, Vives L, Lin J, Turner TN, Santen G, Ruivenkamp C, Kriek M, van Haeringen A, Aten E, Friend K, Liebelt J, Barnett C, Haan E, et al.

Nat Genet. 2017 Apr;49(4):515-526. doi: 10.1038/ng.3792. Epub 2017 Feb 13.

PubMed [citation]

PMID:: 28191889
PMCID:: PMC5374041

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000803755.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a mother and her 2 sons (family 10) and in 6 additional unrelated patients with autosomal dominant intellectual developmental disorder-50 with behavioral abnormalities (MRD50; 617787), Cheng et al. (2018) identified a heterozygous 2-bp deletion (c.239_240delAT, NM_057175.4) in exon 3 of the NAA15 gene, predicted to result in a frameshift and premature termination (His80ArgfsTer17). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was found once in the ExAC database. RT-PCR analysis of patient cells showed reduced mutant mRNA levels, consistent with nonsense-mediated mRNA decay and a loss of function. One of the patients (individual 8) had previously been reported as subject 2 in Stessman et al. (2017).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV001528440.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. A portion of the reported individuals presented cardiovascular defects [PMID 28303347]

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille, SCV002559202.1

#	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	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics Laboratory, University Hospital Schleswig-Holstein, SCV002583438.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002779055.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Daryl Scott Lab, Baylor College of Medicine, SCV003915704.1

#	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	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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