rs33942096

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002292.4(LAMB2):c.1764C>T(p.Pro588Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,613,746 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 33 hom., cov: 32)

Exomes 𝑓: 0.023 ( 430 hom. )

Consequence

LAMB2
NM_002292.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.34

Publications

9 publications found

Variant links:

Genes affected

LAMB2 (HGNC:6487): (laminin subunit beta 2) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 2. The beta 2 chain contains the 7 structural domains typical of beta chains of laminin, including the short alpha region. However, unlike beta 1 chain, beta 2 has a more restricted tissue distribution. It is enriched in the basement membrane of muscles at the neuromuscular junctions, kidney glomerulus and vascular smooth muscle. Transgenic mice in which the beta 2 chain gene was inactivated by homologous recombination, showed defects in the maturation of neuromuscular junctions and impairment of glomerular filtration. Alternative splicing involving a non consensus 5' splice site (gc) in the 5' UTR of this gene has been reported. It was suggested that inefficient splicing of this first intron, which does not change the protein sequence, results in a greater abundance of the unspliced form of the transcript than the spliced form. The full-length nature of the spliced transcript is not known. [provided by RefSeq, Aug 2011]

LAMB2 Gene-Disease associations (from GenCC):

Pierson syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, PanelApp Australia, Orphanet
LAMB2-related infantile-onset nephrotic syndrome
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

LAMB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-49128787-G-A is Benign according to our data. Variant chr3-49128787-G-A is described in ClinVar as [Benign]. Clinvar id is 258600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0162 (2470/152274) while in subpopulation NFE AF = 0.0254 (1726/67996). AF 95% confidence interval is 0.0244. There are 33 homozygotes in GnomAd4. There are 1138 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB2	NM_002292.4 link	c.1764C>T	p.Pro588Pro	synonymous_variant	Exon 14 of 32	ENST00000305544.9	NP_002283.3	P55268
LAMB2	XM_005265127.5 link	c.1764C>T	p.Pro588Pro	synonymous_variant	Exon 15 of 33		XP_005265184.1	P55268

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB2	ENST00000305544.9 link	c.1764C>T	p.Pro588Pro	synonymous_variant	Exon 14 of 32	1	NM_002292.4	ENSP00000307156.4		P55268

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2470

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00360

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0340

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0165

AC:

4141

AN:

251034

AF XY:

0.0163

show subpopulations

Gnomad AFR exome

AF:

0.00339

Gnomad AMR exome

AF:

0.00660

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0317

Gnomad NFE exome

AF:

0.0254

Gnomad OTH exome

AF:

0.0167

GnomAD4 exome

AF:

0.0228

AC:

33359

AN:

1461472

Hom.:

430

Cov.:

AF XY:

0.0222

AC XY:

16108

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.00308

AC:

103

AN:

33478

American (AMR)

AF:

0.00756

AC:

338

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

332

AN:

26122

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39694

South Asian (SAS)

AF:

0.00231

AC:

199

AN:

86252

European-Finnish (FIN)

AF:

0.0319

AC:

1701

AN:

53288

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0266

AC:

29554

AN:

1111770

Other (OTH)

AF:

0.0183

AC:

1108

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

1928

3856

5785

7713

9641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0162

AC:

2470

AN:

152274

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1138

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00358

AC:

149

AN:

41564

American (AMR)

AF:

0.00856

AC:

131

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00269

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0340

AC:

361

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0254

AC:

1726

AN:

67996

Other (OTH)

AF:

0.0138

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

117

234

351

468

585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0216

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0214

EpiControl

AF:

0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pierson syndrome;C3280113:LAMB2-related infantile-onset nephrotic syndrome

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 25, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 12, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 20556798) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kidney disorder

Benign:1

Oct 01, 2018

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

LAMB2-related infantile-onset nephrotic syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Pierson syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.42

PhyloP100

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs33942096

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over