NM_000426.4:c.7760C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000426.4(LAMA2):c.7760C>T(p.Ala2587Val) variant causes a missense change. The variant allele was found at a frequency of 0.695 in 1,612,146 control chromosomes in the GnomAD database, including 393,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31327 hom., cov: 32)

Exomes 𝑓: 0.70 ( 362018 hom. )

Consequence

LAMA2
NM_000426.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.63

Publications

43 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0597179E-5).

BP6

Variant 6-129486484-C-T is Benign according to our data. Variant chr6-129486484-C-T is described in ClinVar as Benign. ClinVar VariationId is 167247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.7760C>T	p.Ala2587Val	missense_variant	Exon 56 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.7748C>T	p.Ala2583Val	missense_variant	Exon 55 of 64		NP_001073291.2
LOC124901401	XR_007059767.1 link	n.-10G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 link	c.7760C>T	p.Ala2587Val	missense_variant	Exon 56 of 65	5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

95962

AN:

151854

Hom.:

31302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.830

Gnomad AMR

AF:

0.670

Gnomad ASJ

AF:

0.737

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.616

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.720

Gnomad OTH

AF:

0.654

GnomAD2 exomes

AF:

0.672

AC:

168513

AN:

250778

AF XY:

0.677

show subpopulations

Gnomad AFR exome

AF:

0.448

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:

1024939

AN:

1460174

Hom.:

362018

Cov.:

AF XY:

0.701

AC XY:

509109

AN XY:

726458

show subpopulations

African (AFR)

AF:

0.446

AC:

14909

AN:

33434

American (AMR)

AF:

0.679

AC:

30366

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

19582

AN:

26118

East Asian (EAS)

AF:

0.628

AC:

24890

AN:

39646

South Asian (SAS)

AF:

0.650

AC:

56013

AN:

86208

European-Finnish (FIN)

AF:

0.641

AC:

34220

AN:

53370

Middle Eastern (MID)

AF:

0.699

AC:

4027

AN:

5762

European-Non Finnish (NFE)

AF:

0.720

AC:

799642

AN:

1110616

Other (OTH)

AF:

0.685

AC:

41290

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

16068

32136

48203

64271

80339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19858

39716

59574

79432

99290

<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:

0.632

AC:

96029

AN:

151972

Hom.:

31327

Cov.:

AF XY:

0.630

AC XY:

46794

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.454

AC:

18821

AN:

41430

American (AMR)

AF:

0.670

AC:

10235

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.737

AC:

2558

AN:

3470

East Asian (EAS)

AF:

0.629

AC:

3250

AN:

5168

South Asian (SAS)

AF:

0.618

AC:

2977

AN:

4816

European-Finnish (FIN)

AF:

0.657

AC:

6924

AN:

10536

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.720

AC:

48911

AN:

67960

Other (OTH)

AF:

0.658

AC:

1389

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1725

3451

5176

6902

8627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.693

Hom.:

154225

Bravo

AF:

0.625

TwinsUK

AF:

0.714

AC:

2648

ALSPAC

AF:

0.724

AC:

2791

ESP6500AA

AF:

0.467

AC:

2058

ESP6500EA

AF:

0.727

AC:

6248

ExAC

AF:

0.667

AC:

81020

Asia WGS

AF:

0.635

AC:

2208

AN:

3478

EpiCase

AF:

0.725

EpiControl

AF:

0.727

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 20, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Merosin deficient congenital muscular dystrophy

Benign:1

May 28, 2019

Mendelics

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.058

.;T;T

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.000011

T;T;T

MetaSVM

Uncertain

0.056

MutationAssessor

Uncertain

2.4

.;.;M

PhyloP100

4.6

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.0

.;.;D

REVEL

Uncertain

0.60

Sift

Benign

0.056

.;.;T

Polyphen

1.0

.;.;D

Vest4

0.58

MPC

0.45

ClinPred

0.017

GERP RS

5.6

Varity_R

0.28

gMVP

0.76

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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