NM_004525.3(LRP2):c.10937G>A (p.Arg3646His) AND Donnai-Barrow syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jul 15, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV001134469.8

Allele description [Variation Report for NM_004525.3(LRP2):c.10937G>A (p.Arg3646His)]

NM_004525.3(LRP2):c.10937G>A (p.Arg3646His)

Gene:

LRP2:LDL receptor related protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.1

Genomic location:

Preferred name:

NM_004525.3(LRP2):c.10937G>A (p.Arg3646His)

HGVS:

NC_000002.12:g.169173996C>T
NG_012634.1:g.193617G>A
NM_004525.3:c.10937G>AMANE SELECT
NP_004516.2:p.Arg3646His
LRG_1300t1:c.10937G>A
LRG_1300:g.193617G>A
LRG_1300p1:p.Arg3646His
NC_000002.10:g.169738752C>T
NC_000002.11:g.170030506C>T
NM_004525.2:c.10937G>A

Protein change:

R3646H

Links:

dbSNP: rs142549310

NCBI 1000 Genomes Browser:

rs142549310

Molecular consequence:

NM_004525.3:c.10937G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Donnai-Barrow syndrome
Synonyms:: Faciooculoacousticorenal syndrome; Diaphragmatic hernia exomphalos absent corpus callosum hypertelorism myopia sensorineural deafness and proteinuria
Identifiers:: MONDO: MONDO:0009104; MedGen: C1857277; Orphanet: 2143; OMIM: 222448

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001294216	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Aug 5, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24406863, 25158045 Citation Link,
SCV001440411	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 1, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002054696	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 15, 2021)	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

SCV001294216

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Aug 5, 2017)

germline

clinical testing

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

Citation Link,

SCV001440411

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 1, 2019)

unknown

clinical testing

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

SCV002054696

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 15, 2021)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	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

Retinoblastoma gene mutations detected by whole exome sequencing of Merkel cell carcinoma.

Cimino PJ, Robirds DH, Tripp SR, Pfeifer JD, Abel HJ, Duncavage EJ.

Mod Pathol. 2014 Aug;27(8):1073-87. doi: 10.1038/modpathol.2013.235. Epub 2014 Jan 10.

PubMed [citation]

PMID:: 24406863

Whole exome sequencing of extreme morbid obesity patients: translational implications for obesity and related disorders.

Paz-Filho G, Boguszewski MC, Mastronardi CA, Patel HR, Johar AS, Chuah A, Huttley GA, Boguszewski CL, Wong ML, Arcos-Burgos M, Licinio J.

Genes (Basel). 2014 Aug 25;5(3):709-25. doi: 10.3390/genes5030709.

PubMed [citation]

PMID:: 25158045
PMCID:: PMC4198926

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001294216.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

#	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 Institute of Human Genetics, University of Leipzig Medical Center, SCV001440411.1

#	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	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002054696.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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