NM_030632.3(ASXL3):c.1978_1981del (p.Asp660fs) AND Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 31, 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:: RCV000059323.5

Allele description [Variation Report for NM_030632.3(ASXL3):c.1978_1981del (p.Asp660fs)]

NM_030632.3(ASXL3):c.1978_1981del (p.Asp660fs)

Gene:

ASXL3:ASXL transcriptional regulator 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_030632.3(ASXL3):c.1978_1981del (p.Asp660fs)

HGVS:

NC_000018.10:g.33739382_33739385del
NG_055244.1:g.165806_165809del
NM_030632.3:c.1978_1981delMANE SELECT
NP_085135.1:p.Asp660fs
NC_000018.9:g.31319346_31319349del
NC_000018.9:g.31319346_31319349delGACA
NM_030632.1:c.1975_1978del
NM_030632.1:c.1978_1981delGACA
NM_030632.3:c.1978_1981delGACAMANE SELECT

Protein change:

D660fs

Links:

OMIM: 615115.0003; dbSNP: rs1555742500

NCBI 1000 Genomes Browser:

rs1555742500

Molecular consequence:

NM_030632.3:c.1978_1981del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome (BRPS)
Synonyms:: Bainbridge-Ropers syndrome
Identifiers:: MONDO: MONDO:0014205; MedGen: C4750837; Orphanet: 352577; OMIM: 615485

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000105901	OMIM	no assertion criteria provided	Pathogenic (Feb 5, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000992738	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 31, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001443562	GenomeConnect - Simons Searchlight	no assertion criteria provided	Pathogenic (May 4, 2018)	de novo	provider interpretation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000105901

OMIM

no assertion criteria provided

Pathogenic
(Feb 5, 2013)

germline

literature only

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

SCV000992738

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 31, 2017)

germline

clinical testing

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

SCV001443562

GenomeConnect - Simons Searchlight

no assertion criteria provided

Pathogenic
(May 4, 2018)

de novo

provider interpretation

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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	de novo	yes	2	not provided	not provided	2	not provided	provider interpretation

Citations

PubMed

De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome.

Bainbridge MN, Hu H, Muzny DM, Musante L, Lupski JR, Graham BH, Chen W, Gripp KW, Jenny K, Wienker TF, Yang Y, Sutton VR, Gibbs RA, Ropers HH.

Genome Med. 2013;5(2):11. doi: 10.1186/gm415.

PubMed [citation]

PMID:: 23383720
PMCID:: PMC3707024

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000105901.2

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

Description

In a child with Bainbridge-Ropers syndrome (BRPS; 615485), Bainbridge et al. (2013) identified a de novo heterozygous 4-bp deletion in the ASXL3 gene resulting in frameshift and premature termination (g.31319343_31319346delACAG, Thr659FsTer41). This patient had mild global hypotonia, normal growth, and global developmental delay with intellectual disability and no speech.

#	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, SCV000992738.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GenomeConnect - Simons Searchlight, SCV001443562.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	provider interpretation	not provided
2	not provided	1	not provided	not provided	provider interpretation	not provided

Description

Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-05-04 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.

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

Last Updated: Jan 7, 2023

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