NM_000212.3(ITGB3):c.777+1G>A AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 4, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001055160.11

Allele description [Variation Report for NM_000212.3(ITGB3):c.777+1G>A]

NM_000212.3(ITGB3):c.777+1G>A

Genes:

LOC130061044:ATAC-STARR-seq lymphoblastoid active region 12308 [Gene]
ITGB3:integrin subunit beta 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.32

Genomic location:

Preferred name:

NM_000212.3(ITGB3):c.777+1G>A

Other names:

NM_000212.3:c.777+1G>A

HGVS:

NC_000017.11:g.47286423G>A
NG_008332.2:g.37582G>A
NM_000212.3:c.777+1G>AMANE SELECT
LRG_481t1:c.777+1G>A
LRG_481:g.37582G>A
NC_000017.10:g.45363789G>A
NC_000017.10:g.45363789G>A
NM_000212.2:c.777+1G>A

Links:

dbSNP: rs745766760

NCBI 1000 Genomes Browser:

rs745766760

Molecular consequence:

NM_000212.3:c.777+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV001219533	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 4, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9215749, 25728920, 16199547, 21917754, 28492532
SCV002067390	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 24, 2019)	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

SCV001219533

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 4, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002067390

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 24, 2019)

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	yes	not provided	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

Hematologically important mutations: Glanzmann thrombasthenia.

French DL, Coller BS.

Blood Cells Mol Dis. 1997;23(1):39-51. No abstract available.

PubMed [citation]

PMID:: 9215749

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

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001219533.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Disruption of this splice site has been observed in individuals with Glanzmann thrombasthenia (PMID: 9215749, 25728920). This variant is present in population databases (rs745766760, gnomAD 0.06%). This sequence change affects a donor splice site in intron 5 of the ITGB3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ITGB3 are known to be pathogenic (PMID: 21917754). This variant is also known as IVS5 +1G>A. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 850886).

#	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 Genetic Services Laboratory, University of Chicago, SCV002067390.1

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

Description

DNA sequence analysis of the ITGB3 gene demonstrated a sequence change in the canonical splice donor site of intron 5, c.777+1G>A. This sequence change has been described in the gnomAD database with a low population frequency of 0.0086% (dbSNP rs745766760). This sequence change is predicted to affect normal splicing of the ITGB3 gene and result in an abnormal protein. This pathogenic sequence change has previously been described in the compound heterozygous state in a patient with Glanzmann thrombasthenia (PMID: 9215749).

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine