6-129401244-A-G

Variant names:

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.5466A>G(p.Glu1822Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,580,252 control chromosomes in the GnomAD database, including 181,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20116 hom., cov: 32)

Exomes 𝑓: 0.47 ( 161602 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.00

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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Myriad Women’s Health
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=-0.49).

BP6

Variant 6-129401244-A-G is Benign according to our data. Variant chr6-129401244-A-G is described in ClinVar as Benign. ClinVar VariationId is 92966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1 with no splicing effect.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	NM_000426.4	MANE Select	c.5466A>G	p.Glu1822Glu	synonymous	Exon 38 of 65	NP_000417.3
	LAMA2	NM_001079823.2		c.5466A>G	p.Glu1822Glu	synonymous	Exon 38 of 64	NP_001073291.2	A0A087WYF1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMA2	ENST00000421865.3	TSL:5 MANE Select	c.5466A>G	p.Glu1822Glu	synonymous	Exon 38 of 65	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5	TSL:5	c.5730A>G	p.Glu1910Glu	synonymous	Exon 39 of 66	ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5	TSL:5	c.5466A>G	p.Glu1822Glu	synonymous	Exon 38 of 64	ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77162

AN:

151922

Hom.:

20073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.486

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.455

Gnomad OTH

AF:

0.498

GnomAD2 exomes

AF:

0.494

AC:

124058

AN:

251072

AF XY:

0.493

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.540

Gnomad EAS exome

AF:

0.573

Gnomad FIN exome

AF:

0.457

Gnomad NFE exome

AF:

0.461

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.469

AC:

670335

AN:

1428212

Hom.:

161602

Cov.:

AF XY:

0.471

AC XY:

335371

AN XY:

712156

show subpopulations

African (AFR)

AF:

0.632

AC:

20684

AN:

32744

American (AMR)

AF:

0.476

AC:

21241

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

13986

AN:

25912

East Asian (EAS)

AF:

0.539

AC:

21266

AN:

39490

South Asian (SAS)

AF:

0.542

AC:

46322

AN:

85530

European-Finnish (FIN)

AF:

0.466

AC:

24822

AN:

53314

Middle Eastern (MID)

AF:

0.513

AC:

2913

AN:

5682

European-Non Finnish (NFE)

AF:

0.454

AC:

490610

AN:

1081534

Other (OTH)

AF:

0.480

AC:

28491

AN:

59346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.407

Heterozygous variant carriers

16204

32408

48611

64815

81019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14620

29240

43860

58480

73100

<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:

0.508

AC:

77275

AN:

152040

Hom.:

20116

Cov.:

AF XY:

0.509

AC XY:

37828

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.619

AC:

25676

AN:

41472

American (AMR)

AF:

0.463

AC:

7073

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1810

AN:

3468

East Asian (EAS)

AF:

0.553

AC:

2861

AN:

5172

South Asian (SAS)

AF:

0.535

AC:

2570

AN:

4806

European-Finnish (FIN)

AF:

0.450

AC:

4757

AN:

10564

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.455

AC:

30891

AN:

67960

Other (OTH)

AF:

0.496

AC:

1049

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1918

3837

5755

7674

9592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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.:

25495

Bravo

AF:

0.514

Asia WGS

AF:

0.514

AC:

1788

AN:

3478

EpiCase

AF:

0.461

EpiControl

AF:

0.464

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Merosin deficient congenital muscular dystrophy (3)

Congenital muscular dystrophy due to partial LAMA2 deficiency (1)

LAMA2-related muscular dystrophy (1)

Muscular dystrophy, limb-girdle, autosomal recessive 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.4

(source)

DANN

Benign

0.71

PhyloP100

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over