NM_030632.3(ASXL3):c.1961_1962insA (p.Ser654_Ser655insTer) AND Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 25, 2023
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:: RCV002810045.3

Allele description [Variation Report for NM_030632.3(ASXL3):c.1961_1962insA (p.Ser654_Ser655insTer)]

NM_030632.3(ASXL3):c.1961_1962insA (p.Ser654_Ser655insTer)

Gene:

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

Variant type:

Insertion

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_030632.3(ASXL3):c.1961_1962insA (p.Ser654_Ser655insTer)

Other names:

NM_030632.3:c.1961_1962insA

HGVS:

NC_000018.10:g.33739365_33739366insA
NG_055244.1:g.165789_165790insA
NM_030632.3:c.1961_1962insAMANE SELECT
NP_085135.1:p.Ser654_Ser655insTer
NC_000018.9:g.31319329_31319330insA

Molecular consequence:

NM_030632.3:c.1961_1962insA - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003761385	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 25, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003761385

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 25, 2023)

germline

curation

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	curation

Citations

PubMed

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761385.1

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

Description

The heterozygous p.Ser655fsTer1 variant in ASXL3 was identified by our study in one individual with autism, poor growth, feeding difficulties, and hypotonia. Trio exome analysis showed this variant to be de novo. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein‚Äôs amino acid sequence beginning at position 655 and leads to a premature termination codon 1 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the ASXL3 gene is an established disease mechanism in Bainbridge-Ropers syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Bainbridge-Ropers syndrome. ACMG/AMP Criteria applied: PVS1, PS2_Moderate, PM2_Supporting (Richards 2015).

#	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: Jun 23, 2024

ClinVar

Relating variation to medicine