NM_031471.6(FERMT3):c.1275del (p.Glu426fs) AND Leukocyte adhesion deficiency 3

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 10, 2010
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000023665.5

Allele description [Variation Report for NM_031471.6(FERMT3):c.1275del (p.Glu426fs)]

NM_031471.6(FERMT3):c.1275del (p.Glu426fs)

Gene:

FERMT3:FERM domain containing kindlin 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_031471.6(FERMT3):c.1275del (p.Glu426fs)

HGVS:

NC_000011.10:g.64220290del
NG_016360.1:g.18611del
NM_001382361.1:c.1275del
NM_001382362.1:c.1287del
NM_001382363.1:c.735del
NM_001382364.1:c.747del
NM_001382448.1:c.1275del
NM_031471.6:c.1275delMANE SELECT
NM_178443.3:c.1287del
NP_001369290.1:p.Glu426fs
NP_001369291.1:p.Glu430fs
NP_001369292.1:p.Glu246fs
NP_001369293.1:p.Glu250fs
NP_001369377.1:p.Glu426fs
NP_113659.3:p.Glu426fs
NP_848537.1:p.Glu430fs
LRG_180:g.18611del
NC_000011.9:g.63987762del
NM_031471.5:c.1275delT

Note:

ClinGen staff contributed the HGVS expression for this variant.

Protein change:

E246fs

Links:

OMIM: 607901.0008; dbSNP: rs775138431

NCBI 1000 Genomes Browser:

rs775138431

Molecular consequence:

NM_001382361.1:c.1275del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001382362.1:c.1287del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001382363.1:c.735del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001382364.1:c.747del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001382448.1:c.1275del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_031471.6:c.1275del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_178443.3:c.1287del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Leukocyte adhesion deficiency 3
Synonyms:: INTEGRIN ACTIVATION DEFICIENCY DISEASE; LEUKOCYTE ADHESION DEFICIENCY 1 VARIANT; Leukocyte adhesion deficiency, type III
Identifiers:: MONDO: MONDO:0013016; MedGen: C2748536; Orphanet: 2968; Orphanet: 99844; OMIM: 612840

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044956	OMIM	no assertion criteria provided	Pathogenic (Jun 10, 2010)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000044956

OMIM

no assertion criteria provided

Pathogenic
(Jun 10, 2010)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Two mutations in the KINDLIN3 gene of a new leukocyte adhesion deficiency III patient reveal distinct effects on leukocyte function in vitro.

McDowall A, Svensson L, Stanley P, Patzak I, Chakravarty P, Howarth K, Sabnis H, Briones M, Hogg N.

Blood. 2010 Jun 10;115(23):4834-42. doi: 10.1182/blood-2009-08-238709. Epub 2010 Mar 31.

PubMed [citation]

PMID:: 20357244

Details of each submission

From OMIM, SCV000044956.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In an 11-month-old African American girl with leukocyte adhesion deficiency type III (LAD3; 612840), McDowall et al. (2010) identified 2 homozygous mutations in the FERMT3 gene. One mutation was a 1-bp deletion (1275delT) in exon 11, resulting in premature termination in the PH domain in the loop between the beta-6 and beta-7 strands. The second homozygous mutation was a G308R substitution (607901.0007). In vitro functional expression assays showed that B cells transfected with the 1275delT mutant protein had no FERMT3 membrane localization and were unable to adhere to ICAM1. The findings indicated that the truncated PH domain was no longer capable of membrane anchoring. The patient's unaffected mother was heterozygous for both mutations, and showed about half-levels of FERMT3 mRNA, consistent with the lack of a functional gene on 1 allele.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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