NM_000212.3(ITGB3):c.224del (p.Cys75fs) AND Glanzmann thrombasthenia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 4, 2020
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV001225301.2

Allele description [Variation Report for NM_000212.3(ITGB3):c.224del (p.Cys75fs)]

NM_000212.3(ITGB3):c.224del (p.Cys75fs)

Gene:

ITGB3:integrin subunit beta 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17q21.32

Genomic location:

Preferred name:

NM_000212.3(ITGB3):c.224del (p.Cys75fs)

HGVS:

NC_000017.11:g.47283412del
NG_008332.2:g.34571del
NM_000212.3:c.224delMANE SELECT
NP_000203.2:p.Cys75fs
LRG_481t1:c.224del
LRG_481:g.34571del
NC_000017.10:g.45360778del
NM_000212.2:c.224del

Protein change:

C75fs

Links:

dbSNP: rs753932639

NCBI 1000 Genomes Browser:

rs753932639

Molecular consequence:

NM_000212.3:c.224del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Glanzmann thrombasthenia
Synonyms:: PLATELET GLYCOPROTEIN IIb-IIIa DEFICIENCY; Thrombasthenia of Glanzmann and Naegeli; Glanzmann thrombasthenia type A; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100326; MedGen: C0040015; Orphanet: 849; OMIM: PS273800

Recent activity

Clear Turn Off Turn On

Homo sapiens cation channel sperm associated 3 (CATSPER3), mRNA
Homo sapiens cation channel sperm associated 3 (CATSPER3), mRNA
gi|1519316004|ref|NM_178019.3|

Nucleotide
cytochrome oxidase subunit 1, partial (mitochondrion) [Camptogramma bilineatum]
cytochrome oxidase subunit 1, partial (mitochondrion) [Camptogramma bilineatum]
gi|2305120492|gb|UXB55542.1|

Protein
cytochrome oxidase subunit 1, partial (mitochondrion) [Zygaena transalpina]
cytochrome oxidase subunit 1, partial (mitochondrion) [Zygaena transalpina]
gi|1557924565|gb|QAA10562.1|

Protein
LOC128772335 [Homo sapiens]
LOC128772335 [Homo sapiens]
Gene ID:128772335

Gene

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
SCV001397583	ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen Platelet ACMG Specifications v2)	Pathogenic (Sep 4, 2020)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 12083483, 25728920 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001397583

ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen

reviewed by expert panel

(ClinGen Platelet ACMG Specifications v2)

Pathogenic
(Sep 4, 2020)

germline

curation

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

Citation Link

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

Glanzmann's thrombasthenia: identification of 19 new mutations in 30 patients.

D'Andrea G, Colaizzo D, Vecchione G, Grandone E, Di Minno G, Margaglione M; GLAnzmann's Thrombasthenia Italian Team (GLATIT)..

Thromb Haemost. 2002 Jun;87(6):1034-42.

PubMed [citation]

PMID:: 12083483

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

Nurden AT, Pillois X, Fiore M, Alessi MC, Bonduel M, Dreyfus M, Goudemand J, Gruel Y, Benabdallah-Guerida S, Latger-Cannard V, Négrier C, Nugent D, Oiron RD, Rand ML, Sié P, Trossaert M, Alberio L, Martins N, Sirvain-Trukniewicz P, Couloux A, Canault M, Fronthroth JP, et al.

Hum Mutat. 2015 May;36(5):548-61. doi: 10.1002/humu.22776.

PubMed [citation]

PMID:: 25728920

Details of each submission

From ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen, SCV001397583.3

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

Description

The ITGB3 c.224del (p.Cys75Leufs) frameshift variant has been reported homozygous in at least 2 GT probands (PMIDs: 25728920, 12083483). It is predicted to undergo NMD due to creation of a premature stop codon in exon 3. The overall allele frequency in gnomAD is extremely low at 0.000003977, with a MAF of 0.000008795 in the non-Finnish European population. In summary, this variant meets criteria to be classified as Pathogenic for GT. GT-specific criteria applied: PVS1,PM2_supporting, PM3, and PP4_strong.

#	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: Aug 13, 2023

ClinVar

Relating variation to medicine