rs56920166

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.6234A>G(p.Lys2078Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,850 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 55 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 48 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.14

Publications

1 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=-0.66).

BP6

Variant 6-129440964-A-G is Benign according to our data. Variant chr6-129440964-A-G is described in ClinVar as Benign. ClinVar VariationId is 129440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.14 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.6234A>G	p.Lys2078Lys	synonymous_variant	Exon 43 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.6234A>G	p.Lys2078Lys	synonymous_variant	Exon 43 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
LAMA2	ENST00000421865.3 link	c.6234A>G	p.Lys2078Lys	synonymous_variant	Exon 43 of 65	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5 link	c.6498A>G	p.Lys2166Lys	synonymous_variant	Exon 44 of 66	5		ENSP00000480802.2
LAMA2	ENST00000617695.5 link	c.6234A>G	p.Lys2078Lys	synonymous_variant	Exon 43 of 64	5		ENSP00000481744.2
ENSG00000226149	ENST00000665046.1 link	n.1264T>C		non_coding_transcript_exon_variant	Exon 10 of 10

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2066

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00353

AC:

885

AN:

250930

AF XY:

0.00244

show subpopulations

Gnomad AFR exome

AF:

0.0502

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00140

AC:

2046

AN:

1461586

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

904

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.0522

AC:

1746

AN:

33458

American (AMR)

AF:

0.00199

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000288

AC:

AN:

1111824

Other (OTH)

AF:

0.00278

AC:

168

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

101

202

303

404

505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0136

AC:

2066

AN:

152264

Hom.:

Cov.:

AF XY:

0.0134

AC XY:

1001

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0472

AC:

1961

AN:

41538

American (AMR)

AF:

0.00477

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68018

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

190

286

381

476

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:

0.00625

Hom.:

Bravo

AF:

0.0157

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 25, 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.

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

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.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.48

PhyloP100

3.1

Mutation Taster

=100/0

polymorphism

(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