NM_001130004.2(ACTN1):c.2255G>A (p.Arg752Gln) AND Platelet-type bleeding disorder 15

Germline classification:: Uncertain significance (2 submissions)
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:: RCV000034868.30

Allele description [Variation Report for NM_001130004.2(ACTN1):c.2255G>A (p.Arg752Gln)]

NM_001130004.2(ACTN1):c.2255G>A (p.Arg752Gln)

Gene:

ACTN1:actinin alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.1

Genomic location:

Preferred name:

NM_001130004.2(ACTN1):c.2255G>A (p.Arg752Gln)

HGVS:

NC_000014.9:g.68879987C>T
NG_029480.1:g.104380G>A
NM_001102.4:c.2255G>A
NM_001130004.1:c.2255G>A
NM_001130004.2:c.2255G>AMANE SELECT
NM_001130005.2:c.2255G>A
NP_001093.1:p.Arg752Gln
NP_001123476.1:p.Arg752Gln
NP_001123477.1:p.Arg752Gln
LRG_886t1:c.2255G>A
LRG_886:g.104380G>A
NC_000014.8:g.69346704C>T
NM_001102.3:c.2255G>A
P12814:p.Arg752Gln

Protein change:

R752Q; ARG752GLN

Links:

UniProtKB: P12814#VAR_069916; OMIM: 102575.0003; dbSNP: rs387907347

NCBI 1000 Genomes Browser:

rs387907347

Molecular consequence:

NM_001102.4:c.2255G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130004.2:c.2255G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130005.2:c.2255G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Platelet-type bleeding disorder 15 (BDPLT15)
Synonyms:: MACROTHROMBOCYTOPENIA, AUTOSOMAL DOMINANT, ACTN1-RELATED
Identifiers:: MONDO: MONDO:0014078; MedGen: C3554663; Orphanet: 140957; OMIM: 615193

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
SCV000058472	OMIM	no assertion criteria provided	Pathogenic (Mar 7, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004013089	ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance	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

SCV000058472

OMIM

no assertion criteria provided

Pathogenic
(Mar 7, 2013)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004013089

ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance

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	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

ACTN1 mutations cause congenital macrothrombocytopenia.

Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, Chiba K, Tanaka H, Miyazaki K, Sakai M, Ohtake M, Kobayashi R, Iguchi A, Niimi G, Otsu M, Takahashi Y, Miyano S, Saito H, Kojima S, Ogawa S.

Am J Hum Genet. 2013 Mar 7;92(3):431-8. doi: 10.1016/j.ajhg.2013.01.015. Epub 2013 Feb 21.

PubMed [citation]

PMID:: 23434115
PMCID:: PMC3591851

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000058472.1

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

Description

In a Japanese mother and son with BDPLT15 (615193) manifest as macrothrombocytopenia, Kunishima et al. (2013) identified a heterozygous 2255G-A transition in exon 18 of the ACTN1 gene, resulting in an arg752-to-gln (R752Q) substitution at a highly conserved residue in the functional C-terminal calmodulin-like domain. The mutation, which was identified by sequencing, was not found in several large control databases or in 120 control individuals.

#	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

From ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology, SCV004013089.1

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

#	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		1	not provided	not provided	not provided

Last Updated: May 7, 2024

ClinVar

Relating variation to medicine