NM_005413.4(SIX3):c.126_173del (p.Gly43_Gly58del) AND Holoprosencephaly 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 13, 2024
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:: RCV002050118.3

Allele description [Variation Report for NM_005413.4(SIX3):c.126_173del (p.Gly43_Gly58del)]

NM_005413.4(SIX3):c.126_173del (p.Gly43_Gly58del)

Gene:

SIX3:SIX homeobox 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_005413.4(SIX3):c.126_173del (p.Gly43_Gly58del)

HGVS:

NC_000002.12:g.44942230_44942277del
NG_016222.1:g.5333_5380del
NM_005413.4:c.126_173delMANE SELECT
NP_005404.1:p.Gly43_Gly58del
NC_000002.11:g.45169337_45169384del
NC_000002.11:g.45169369_45169416del

Links:

dbSNP: rs747291764

NCBI 1000 Genomes Browser:

rs747291764

Molecular consequence:

NM_005413.4:c.126_173del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: Holoprosencephaly 2 (HPE2)
Identifiers:: MONDO: MONDO:0007999; MedGen: C1834877; Orphanet: 2162; OMIM: 157170

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002112590	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002112590

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2024)

germline

clinical testing

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	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, SCV002112590.2

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

Description

This variant, c.126_173del, results in the deletion of 16 amino acid(s) of the SIX3 protein (p.Gly43_Gly58del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SIX3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1346455). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

#	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

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