rs3749878

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_StrongBP7BA1

The NM_000426.4(LAMA2):c.5502G>A(p.Glu1834Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,600,776 control chromosomes in the GnomAD database, including 183,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20023 hom., cov: 32)

Exomes 𝑓: 0.47 ( 163053 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.662

Publications

19 publications found

Variant links:

Genes affected

LAMA2 (HGNC:6482): (laminin subunit alpha 2) Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. It is composed of three subunits, alpha, beta, and gamma, which are bound to each other by disulfide bonds into a cross-shaped molecule. This gene encodes the alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). Mutations in this gene have been identified as the cause of congenital merosin-deficient muscular dystrophy. Two transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

LAMA2 Gene-Disease associations (from GenCC):

congenital merosin-deficient muscular dystrophy 1A
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
LAMA2-related muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy, limb-girdle, autosomal recessive 23
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LAMA2 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=-0.71).

BP6

Variant 6-129401280-G-A is Benign according to our data. Variant chr6-129401280-G-A is described in ClinVar as Benign. ClinVar VariationId is 92967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.662 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.5502G>A	p.Glu1834Glu	synonymous_variant	Exon 38 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.5502G>A	p.Glu1834Glu	synonymous_variant	Exon 38 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA2	ENST00000421865.3 link	c.5502G>A	p.Glu1834Glu	synonymous_variant	Exon 38 of 65	5	NM_000426.4	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5 link	c.5766G>A	p.Glu1922Glu	synonymous_variant	Exon 39 of 66	5		ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5 link	c.5502G>A	p.Glu1834Glu	synonymous_variant	Exon 38 of 64	5		ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76955

AN:

151890

Hom.:

19980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.619

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.496

GnomAD2 exomes

AF:

0.493

AC:

123635

AN:

250918

AF XY:

0.492

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.540

Gnomad EAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.470

AC:

681074

AN:

1448768

Hom.:

163053

Cov.:

AF XY:

0.471

AC XY:

340054

AN XY:

721386

show subpopulations

African (AFR)

AF:

0.633

AC:

21003

AN:

33186

American (AMR)

AF:

0.475

AC:

21229

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

14071

AN:

26040

East Asian (EAS)

AF:

0.533

AC:

21092

AN:

39606

South Asian (SAS)

AF:

0.542

AC:

46606

AN:

85968

European-Finnish (FIN)

AF:

0.462

AC:

24642

AN:

53346

Middle Eastern (MID)

AF:

0.513

AC:

2949

AN:

5748

European-Non Finnish (NFE)

AF:

0.455

AC:

500658

AN:

1100166

Other (OTH)

AF:

0.480

AC:

28824

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

18004

36008

54012

72016

90020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15078

30156

45234

60312

75390

<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:

0.507

AC:

77068

AN:

152008

Hom.:

20023

Cov.:

AF XY:

0.508

AC XY:

37718

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.619

AC:

25674

AN:

41456

American (AMR)

AF:

0.462

AC:

7054

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1810

AN:

3468

East Asian (EAS)

AF:

0.551

AC:

2853

AN:

5178

South Asian (SAS)

AF:

0.534

AC:

2576

AN:

4822

European-Finnish (FIN)

AF:

0.447

AC:

4723

AN:

10560

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30761

AN:

67938

Other (OTH)

AF:

0.494

AC:

1045

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1939

3878

5816

7755

9694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.475

Hom.:

73611

Bravo

AF:

0.513

Asia WGS

AF:

0.512

AC:

1783

AN:

3478

EpiCase

AF:

0.460

EpiControl

AF:

0.463

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 18, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 25, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Merosin deficient congenital muscular dystrophy

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

LAMA2-related muscular dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital muscular dystrophy due to partial LAMA2 deficiency

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. -

Muscular dystrophy, limb-girdle, autosomal recessive 23

Benign:1

Aug 19, 2021

Genome-Nilou Lab

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

-0.71

CADD

Benign

1.7

(source)

DANN

Benign

0.90

PhyloP100

-0.66

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

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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