NM_002180.3(IGHMBP2):c.1808G>A (p.Arg603His) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 12, 2024
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:: RCV000224756.4

Allele description [Variation Report for NM_002180.3(IGHMBP2):c.1808G>A (p.Arg603His)]

NM_002180.3(IGHMBP2):c.1808G>A (p.Arg603His)

Gene:

IGHMBP2:immunoglobulin mu DNA binding protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.3

Genomic location:

Preferred name:

NM_002180.3(IGHMBP2):c.1808G>A (p.Arg603His)

HGVS:

NC_000011.10:g.68936288G>A
NG_007976.1:g.37438G>A
NM_002180.3:c.1808G>AMANE SELECT
NP_002171.2:p.Arg603His
NP_002171.2:p.Arg603His
LRG_250t1:c.1808G>A
LRG_250:g.37438G>A
LRG_250p1:p.Arg603His
NC_000011.9:g.68703756G>A
NM_002180.2:c.1808G>A
P38935:p.Arg603His

Protein change:

R603H

Links:

UniProtKB: P38935#VAR_022337; dbSNP: rs151079750

NCBI 1000 Genomes Browser:

rs151079750

Molecular consequence:

NM_002180.3:c.1808G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000281632	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 5, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005201165	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 12, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000281632

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 5, 2017)

germline

clinical testing

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

SCV005201165

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 12, 2024)

germline

clinical testing

Citation Link

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	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000281632.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	not provided	not provided	not provided	not provided		not provided	0.000416	not provided	not provided

From GeneDx, SCV005201165.1

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

Description

Reported previously in an individual with spinal muscular atrophy with respiratory distress type 1 who harbored a second IGHMBP2 variant (PMID: 14681881); Functional studies indicate that R603H severely reduces ATPase activity and impairs unwinding activity on RNA duplices (PMID: 19158098); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 14681881, 22965130, 32376792, 25473036, 24388491, 25439726, 19158098)

#	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

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