rs34290943

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002292.4(LAMB2):c.3387A>G(p.Gln1129Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,614,016 control chromosomes in the GnomAD database, including 12,493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 931 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11562 hom. )

Consequence

LAMB2
NM_002292.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.789

Publications

21 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=-0.6).

BP6

Variant 3-49124227-T-C is Benign according to our data. Variant chr3-49124227-T-C is described in ClinVar as Benign. ClinVar VariationId is 258608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.789 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB2	NM_002292.4 link	c.3387A>G	p.Gln1129Gln	synonymous_variant	Exon 23 of 32	ENST00000305544.9	NP_002283.3
LAMB2	XM_005265127.5 link	c.3387A>G	p.Gln1129Gln	synonymous_variant	Exon 24 of 33		XP_005265184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMB2	ENST00000305544.9 link	c.3387A>G	p.Gln1129Gln	synonymous_variant	Exon 23 of 32	1	NM_002292.4	ENSP00000307156.4

Frequencies

GnomAD3 genomes

AF:

0.0920

AC:

13994

AN:

152154

Hom.:

930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0670

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0788

GnomAD2 exomes

AF:

0.109

AC:

27299

AN:

251184

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.0171

Gnomad AMR exome

AF:

0.0512

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.118

AC:

172833

AN:

1461744

Hom.:

11562

Cov.:

AF XY:

0.120

AC XY:

87401

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.0162

AC:

543

AN:

33480

American (AMR)

AF:

0.0518

AC:

2318

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

6103

AN:

26136

East Asian (EAS)

AF:

0.00118

AC:

AN:

39700

South Asian (SAS)

AF:

0.158

AC:

13619

AN:

86254

European-Finnish (FIN)

AF:

0.170

AC:

9048

AN:

53316

Middle Eastern (MID)

AF:

0.160

AC:

920

AN:

5768

European-Non Finnish (NFE)

AF:

0.120

AC:

132927

AN:

1111978

Other (OTH)

AF:

0.121

AC:

7308

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

10663

21326

31989

42652

53315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4750

9500

14250

19000

23750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0919

AC:

13992

AN:

152272

Hom.:

931

Cov.:

AF XY:

0.0953

AC XY:

7092

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0190

AC:

791

AN:

41584

American (AMR)

AF:

0.0669

AC:

1024

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

812

AN:

3470

East Asian (EAS)

AF:

0.00309

AC:

AN:

5170

South Asian (SAS)

AF:

0.145

AC:

703

AN:

4832

European-Finnish (FIN)

AF:

0.188

AC:

1995

AN:

10602

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8393

AN:

67988

Other (OTH)

AF:

0.0784

AC:

166

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

637

1275

1912

2550

3187

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.118

Hom.:

687

Bravo

AF:

0.0760

Asia WGS

AF:

0.0610

AC:

217

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.116

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 01, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

LAMB2-related infantile-onset nephrotic syndrome

Benign:1

Jan 13, 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 13, 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

-0.60

CADD

Benign

3.0

(source)

DANN

Benign

0.56

PhyloP100

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=90/10

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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