NM_000426.4:c.8691A>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.8691A>G(p.Arg2897Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,613,018 control chromosomes in the GnomAD database, including 122 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. R2897R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.015 ( 59 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 63 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.288

Publications

0 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=-0.5).

BP6

Variant 6-129505343-A-G is Benign according to our data. Variant chr6-129505343-A-G is described in ClinVar as Benign. ClinVar VariationId is 129446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.288 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	NM_000426.4	MANE Select	c.8691A>G	p.Arg2897Arg	synonymous	Exon 61 of 65	NP_000417.3
	LAMA2	NM_001079823.2		c.8679A>G	p.Arg2893Arg	synonymous	Exon 60 of 64	NP_001073291.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LAMA2	ENST00000421865.3	TSL:5 MANE Select	c.8691A>G	p.Arg2897Arg	synonymous	Exon 61 of 65	ENSP00000400365.2
LAMA2	ENST00000618192.5	TSL:5	c.8955A>G	p.Arg2985Arg	synonymous	Exon 62 of 66	ENSP00000480802.2
LAMA2	ENST00000617695.5	TSL:5	c.8679A>G	p.Arg2893Arg	synonymous	Exon 60 of 64	ENSP00000481744.2

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2301

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00407

AC:

1022

AN:

251244

AF XY:

0.00299

show subpopulations

Gnomad AFR exome

AF:

0.0542

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00156

AC:

2280

AN:

1460712

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

934

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.0549

AC:

1837

AN:

33432

American (AMR)

AF:

0.00382

AC:

171

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000116

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000459

AC:

AN:

1110990

Other (OTH)

AF:

0.00326

AC:

197

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

102

204

307

409

511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.0152

AC:

2313

AN:

152306

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1067

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0518

AC:

2153

AN:

41562

American (AMR)

AF:

0.00804

AC:

123

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68028

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

110

220

329

439

549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0130

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Congenital muscular dystrophy due to partial LAMA2 deficiency (1)

LAMA2-related muscular dystrophy (1)

Merosin deficient congenital muscular dystrophy;C4748327:Muscular dystrophy, limb-girdle, autosomal recessive 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.8

(source)

DANN

Benign

0.71

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over