NM_002292.4(LAMB2):c.4510_4552del (p.Gln1504fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 2022
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:: RCV001044619.4

Allele description [Variation Report for NM_002292.4(LAMB2):c.4510_4552del (p.Gln1504fs)]

NM_002292.4(LAMB2):c.4510_4552del (p.Gln1504fs)

Gene:

LAMB2:laminin subunit beta 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_002292.4(LAMB2):c.4510_4552del (p.Gln1504fs)

HGVS:

NC_000003.12:g.49122727_49122769del
NG_008094.1:g.15400_15442del
NG_054716.1:g.3172_3214del
NM_002292.4:c.4510_4552delMANE SELECT
NP_002283.3:p.Gln1504fs
NC_000003.11:g.49160158_49160200del
NC_000003.11:g.49160160_49160202del
NM_002292.3:c.4510_4552del

Protein change:

Q1504fs

Links:

dbSNP: rs2045352880

NCBI 1000 Genomes Browser:

rs2045352880

Molecular consequence:

NM_002292.4:c.4510_4552del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Pierson syndrome
Synonyms:: Microcoria and congenital nephrotic syndrome; MICROCORIA-CONGENITAL NEPHROTIC SYNDROME
Identifiers:: MONDO: MONDO:0012184; MedGen: C1836876; Orphanet: 2670; OMIM: 609049

Name:: LAMB2-related infantile-onset nephrotic syndrome
Synonyms:: Nephrotic syndrome, type 5, with or without ocular abnormalities; NEPHROTIC SYNDROME, TYPE 5, WITHOUT OCULAR ABNORMALITIES; NEPHROTIC SYNDROME, TYPE 5, WITH OCULAR ABNORMALITIES
Identifiers:: MONDO: MONDO:0013621; MedGen: C3280113; Orphanet: 306507; OMIM: 614199

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001208424	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 26, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15367484, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001208424

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 26, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities.

Zenker M, Aigner T, Wendler O, Tralau T, Müntefering H, Fenski R, Pitz S, Schumacher V, Royer-Pokora B, Wühl E, Cochat P, Bouvier R, Kraus C, Mark K, Madlon H, Dötsch J, Rascher W, Maruniak-Chudek I, Lennert T, Neumann LM, Reis A.

Hum Mol Genet. 2004 Nov 1;13(21):2625-32. Epub 2004 Sep 14.

PubMed [citation]

PMID:: 15367484

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001208424.4

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

Description

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: 842232). This variant has not been reported in the literature in individuals affected with LAMB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1504Valfs*2) in the LAMB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMB2 are known to be pathogenic (PMID: 15367484).

#	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

Last Updated: Apr 15, 2024

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