NM_002292.4(LAMB2):c.3521A>C (p.Asp1174Ala) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 11, 2019
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:: RCV001212817.1

Allele description [Variation Report for NM_002292.4(LAMB2):c.3521A>C (p.Asp1174Ala)]

NM_002292.4(LAMB2):c.3521A>C (p.Asp1174Ala)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_002292.4(LAMB2):c.3521A>C (p.Asp1174Ala)

HGVS:

NC_000003.12:g.49124004T>G
NG_008094.1:g.14163A>C
NG_054716.1:g.1935A>C
NM_002292.4:c.3521A>CMANE SELECT
NP_002283.3:p.Asp1174Ala
NC_000003.11:g.49161437T>G
NM_002292.3:c.3521A>C

Protein change:

D1174A

Links:

dbSNP: rs765996794

NCBI 1000 Genomes Browser:

rs765996794

Molecular consequence:

NM_002292.4:c.3521A>C - missense variant - [Sequence Ontology: SO:0001583]

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

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
SCV001384415	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 11, 2019)	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

SCV001384415

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 11, 2019)

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

Citations

PubMed

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, SCV001384415.1

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

Description

This sequence change replaces aspartic acid with alanine at codon 1174 of the LAMB2 protein (p.Asp1174Ala). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and alanine. This variant is present in population databases (rs765996794, ExAC 0.009%). This variant has not been reported in the literature in individuals with LAMB2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine