chr6-129486569-G-A

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.7845G>A(p.Pro2615Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,613,270 control chromosomes in the GnomAD database, including 67,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10420 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57191 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.698

Publications

22 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:

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=-0.61).

BP6

Variant 6-129486569-G-A is Benign according to our data. Variant chr6-129486569-G-A is described in ClinVar as Benign. ClinVar VariationId is 92988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.698 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 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.7845G>A	p.Pro2615Pro	synonymous	Exon 56 of 65	NP_000417.3
	LAMA2	NM_001079823.2		c.7833G>A	p.Pro2611Pro	synonymous	Exon 55 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.7845G>A	p.Pro2615Pro	synonymous	Exon 56 of 65	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5	TSL:5	c.8109G>A	p.Pro2703Pro	synonymous	Exon 57 of 66	ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5	TSL:5	c.7833G>A	p.Pro2611Pro	synonymous	Exon 55 of 64	ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53024

AN:

151958

Hom.:

10404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.319

GnomAD2 exomes

AF:

0.304

AC:

76308

AN:

251054

AF XY:

0.298

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.306

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.274

AC:

400241

AN:

1461194

Hom.:

57191

Cov.:

AF XY:

0.274

AC XY:

199329

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.549

AC:

18374

AN:

33466

American (AMR)

AF:

0.305

AC:

13645

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5370

AN:

26132

East Asian (EAS)

AF:

0.372

AC:

14744

AN:

39662

South Asian (SAS)

AF:

0.308

AC:

26581

AN:

86250

European-Finnish (FIN)

AF:

0.321

AC:

17161

AN:

53414

Middle Eastern (MID)

AF:

0.269

AC:

1550

AN:

5764

European-Non Finnish (NFE)

AF:

0.257

AC:

285201

AN:

1111420

Other (OTH)

AF:

0.292

AC:

17615

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

17084

34168

51253

68337

85421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9858

19716

29574

39432

49290

<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:

0.349

AC:

53077

AN:

152076

Hom.:

10420

Cov.:

AF XY:

0.350

AC XY:

25989

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.539

AC:

22343

AN:

41470

American (AMR)

AF:

0.313

AC:

4788

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

737

AN:

3472

East Asian (EAS)

AF:

0.371

AC:

1913

AN:

5160

South Asian (SAS)

AF:

0.348

AC:

1675

AN:

4816

European-Finnish (FIN)

AF:

0.302

AC:

3199

AN:

10584

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.258

AC:

17523

AN:

67974

Other (OTH)

AF:

0.314

AC:

665

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1686

3372

5058

6744

8430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.288

Hom.:

6245

Bravo

AF:

0.359

Asia WGS

AF:

0.348

AC:

1211

AN:

3478

EpiCase

AF:

0.250

EpiControl

AF:

0.248

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Merosin deficient congenital muscular dystrophy (2)

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

-0.61

CADD

Benign

6.6

(source)

DANN

Benign

0.85

PhyloP100

-0.70

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over