NM_015338.6(ASXL1):c.3194G>A (p.Trp1065Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 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:: RCV001922107.6

Allele description [Variation Report for NM_015338.6(ASXL1):c.3194G>A (p.Trp1065Ter)]

NM_015338.6(ASXL1):c.3194G>A (p.Trp1065Ter)

Gene:

ASXL1:ASXL transcriptional regulator 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q11.21

Genomic location:

Preferred name:

NM_015338.6(ASXL1):c.3194G>A (p.Trp1065Ter)

HGVS:

NC_000020.11:g.32435906G>A
NG_027868.1:g.82563G>A
NM_001363734.1:c.3011G>A
NM_015338.6:c.3194G>AMANE SELECT
NP_001350663.1:p.Trp1004Ter
NP_056153.2:p.Trp1065Ter
LRG_630:g.82563G>A
NC_000020.10:g.31023709G>A

Protein change:

W1004*

Links:

dbSNP: rs2145378635

NCBI 1000 Genomes Browser:

rs2145378635

Molecular consequence:

NM_001363734.1:c.3011G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_015338.6:c.3194G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV002149133	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30806792, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002149133

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 1, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Exploring by whole exome sequencing patients with initial diagnosis of Rubinstein-Taybi syndrome: the interconnections of epigenetic machinery disorders.

Negri G, Magini P, Milani D, Crippa M, Biamino E, Piccione M, Sotgiu S, Perrìa C, Vitiello G, Frontali M, Boni A, Di Fede E, Gandini MC, Colombo EA, Bamshad MJ, Nickerson DA, Smith JD, Loddo I, Finelli P, Seri M, Pippucci T, Larizza L, et al.

Hum Genet. 2019 Mar;138(3):257-269. doi: 10.1007/s00439-019-01985-y. Epub 2019 Feb 26.

PubMed [citation]

PMID:: 30806792
PMCID:: PMC6736609

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002149133.3

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

Description

ClinVar contains an entry for this variant (Variation ID: 1381947). This variant has not been reported in the literature in individuals affected with ASXL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp1065*) in the ASXL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 477 amino acid(s) of the ASXL1 protein. This variant disrupts a region of the ASXL1 protein in which other variant(s) (p.Arg1415*) have been determined to be pathogenic (PMID: 30806792). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been 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: Sep 29, 2024

ClinVar

Relating variation to medicine