rs2229849

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.7830G>C(p.Val2610Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 1,613,552 control chromosomes in the GnomAD database, including 393,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V2610V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.63 ( 31394 hom., cov: 32)

Exomes 𝑓: 0.70 ( 362196 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.250

Publications

21 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:

ENSG00000226149 (HGNC:):

ENSG00000226149 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=-0.84).

BP6

Variant 6-129486554-G-C is Benign according to our data. Variant chr6-129486554-G-C is described in ClinVar as Benign. ClinVar VariationId is 92987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
LAMA2	NM_000426.4 link	c.7830G>C	p.Val2610Val	synonymous_variant	Exon 56 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.7818G>C	p.Val2606Val	synonymous_variant	Exon 55 of 64		NP_001073291.2
LOC124901401	XR_007059767.1 link	n.-80C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 link	c.7830G>C	p.Val2610Val	synonymous_variant	Exon 56 of 65	5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96110

AN:

151912

Hom.:

31368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.830

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.627

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.656

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.656

GnomAD2 exomes

AF:

0.672

AC:

168758

AN:

251018

AF XY:

0.677

show subpopulations

Gnomad AFR exome

AF:

0.451

Gnomad AMR exome

AF:

0.677

Gnomad ASJ exome

AF:

0.750

Gnomad EAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.646

Gnomad NFE exome

AF:

0.717

Gnomad OTH exome

AF:

0.684

GnomAD4 exome

AF:

0.702

AC:

1025847

AN:

1461522

Hom.:

362196

Cov.:

AF XY:

0.701

AC XY:

509515

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.448

AC:

15009

AN:

33468

American (AMR)

AF:

0.679

AC:

30375

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

19590

AN:

26132

East Asian (EAS)

AF:

0.628

AC:

24896

AN:

39654

South Asian (SAS)

AF:

0.650

AC:

56041

AN:

86256

European-Finnish (FIN)

AF:

0.641

AC:

34246

AN:

53416

Middle Eastern (MID)

AF:

0.699

AC:

4029

AN:

5766

European-Non Finnish (NFE)

AF:

0.720

AC:

800323

AN:

1111732

Other (OTH)

AF:

0.685

AC:

41338

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

15894

31788

47681

63575

79469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19886

39772

59658

79544

99430

<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:

0.633

AC:

96179

AN:

152030

Hom.:

31394

Cov.:

AF XY:

0.631

AC XY:

46838

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.457

AC:

18942

AN:

41436

American (AMR)

AF:

0.670

AC:

10245

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

2559

AN:

3472

East Asian (EAS)

AF:

0.627

AC:

3235

AN:

5158

South Asian (SAS)

AF:

0.619

AC:

2983

AN:

4818

European-Finnish (FIN)

AF:

0.656

AC:

6930

AN:

10560

Middle Eastern (MID)

AF:

0.714

AC:

210

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48921

AN:

67974

Other (OTH)

AF:

0.661

AC:

1397

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1750

3499

5249

6998

8748

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.702

Hom.:

12240

Bravo

AF:

0.626

Asia WGS

AF:

0.636

AC:

2211

AN:

3478

EpiCase

AF:

0.725

EpiControl

AF:

0.727

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Jan 20, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 05, 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. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 20, 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

- -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Merosin deficient congenital muscular dystrophy

Benign:3

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 13, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

-0.84

CADD

Benign

0.81

(source)

DANN

Benign

0.68

PhyloP100

-0.25

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