NM_002107.7(H3-3A):c.52A>G (p.Arg18Gly) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 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:: RCV003107859.6

Allele description [Variation Report for NM_002107.7(H3-3A):c.52A>G (p.Arg18Gly)]

NM_002107.7(H3-3A):c.52A>G (p.Arg18Gly)

Gene:

H3-3A:H3.3 histone A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.12

Genomic location:

Preferred name:

NM_002107.7(H3-3A):c.52A>G (p.Arg18Gly)

Other names:

H3F3A, ARG18GLY

HGVS:

NC_000001.11:g.226064403A>G
NG_065173.1:g.6697A>G
NM_001379043.1:c.52A>G
NM_001379045.1:c.52A>G
NM_001379046.1:c.52A>G
NM_001379047.1:c.52A>G
NM_002107.7:c.52A>GMANE SELECT
NP_001365972.1:p.Arg18Gly
NP_001365974.1:p.Arg18Gly
NP_001365975.1:p.Arg18Gly
NP_001365976.1:p.Arg18Gly
NP_002098.1:p.Arg18Gly
LRG_1410t1:c.52A>G
LRG_1410:g.6697A>G
LRG_1410p1:p.Arg18Gly
NC_000001.10:g.226252104A>G
NM_002107.4:c.52A>G

Protein change:

R18G; ARG18GLY

Links:

OMIM: 601128.0001; dbSNP: rs2102735576

NCBI 1000 Genomes Browser:

rs2102735576

Molecular consequence:

NM_001379043.1:c.52A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001379045.1:c.52A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001379046.1:c.52A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001379047.1:c.52A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002107.7:c.52A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003783235	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 26, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33268356, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003783235

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 26, 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

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.

Bryant L, Li D, Cox SG, Marchione D, Joiner EF, Wilson K, Janssen K, Lee P, March ME, Nair D, Sherr E, Fregeau B, Wierenga KJ, Wadley A, Mancini GMS, Powell-Hamilton N, van de Kamp J, Grebe T, Dean J, Ross A, Crawford HP, Powis Z, et al.

Sci Adv. 2020 Dec 2;6(49). doi: 10.1126/sciadv.abc9207. Print 2020 Dec.

PubMed [citation]

PMID:: 33268356
PMCID:: PMC7821880

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, SCV003783235.4

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

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 18 of the H3F3A protein (p.Arg18Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Bryant-Li-Bhoj neurodevelopmental syndrome (PMID: 33268356). In at least one individual the variant was observed to be de novo. This variant is also known as p.R17G. ClinVar contains an entry for this variant (Variation ID: 1339283). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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: Feb 25, 2025

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