NM_018263.6(ASXL2):c.3995A>G (p.Asn1332Ser) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 1, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV002631069.14

Allele description [Variation Report for NM_018263.6(ASXL2):c.3995A>G (p.Asn1332Ser)]

NM_018263.6(ASXL2):c.3995A>G (p.Asn1332Ser)

Gene:

ASXL2:ASXL transcriptional regulator 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_018263.6(ASXL2):c.3995A>G (p.Asn1332Ser)

HGVS:

NC_000002.12:g.25742342T>C
NG_052995.1:g.141175A>G
NM_001369346.1:c.3821A>G
NM_001369347.1:c.3215A>G
NM_018263.6:c.3995A>GMANE SELECT
NP_001356275.1:p.Asn1274Ser
NP_001356276.1:p.Asn1072Ser
NP_060733.4:p.Asn1332Ser
LRG_1421t1:c.3995A>G
LRG_1421:g.141175A>G
LRG_1421p1:p.Asn1332Ser
NC_000002.11:g.25965211T>C

Protein change:

N1072S

Molecular consequence:

NM_001369346.1:c.3821A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369347.1:c.3215A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_018263.6:c.3995A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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342108[uid] (1)
Taxonomy
Papilionoidea cytochrome oxidase subunit I gene, partial cds; mitochondrial.
Papilionoidea cytochrome oxidase subunit I gene, partial cds; mitochondrial.
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002968305	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004138710	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Sep 1, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002968305

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 13, 2022)

germline

clinical testing

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

SCV004138710

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely benign
(Sep 1, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, SCV002968305.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ASXL2-related conditions. This variant is present in population databases (rs775329935, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1332 of the ASXL2 protein (p.Asn1332Ser).

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV004138710.10

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

Description

ASXL2: BS2

#	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		1	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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