NM_000426.4:c.6237G>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.6237G>A(p.Thr2079Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,612,810 control chromosomes in the GnomAD database, including 21,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2159 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19787 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.70

Publications

16 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=-0.56).

BP6

Variant 6-129440967-G-A is Benign according to our data. Variant chr6-129440967-G-A is described in ClinVar as Benign. ClinVar VariationId is 92975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA2	ENST00000421865.3 link	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 65	5	NM_000426.4	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5 link	c.6501G>A	p.Thr2167Thr	synonymous_variant	Exon 44 of 66	5		ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5 link	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 64	5		ENSP00000481744.2	A0A087WYF1
ENSG00000226149	ENST00000665046.1 link	n.1261C>T		non_coding_transcript_exon_variant	Exon 10 of 10

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24773

AN:

152000

Hom.:

2159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.163

GnomAD2 exomes

AF:

0.173

AC:

43412

AN:

250786

AF XY:

0.171

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.163

AC:

237679

AN:

1460692

Hom.:

19787

Cov.:

AF XY:

0.163

AC XY:

118245

AN XY:

726738

show subpopulations

African (AFR)

AF:

0.133

AC:

4439

AN:

33460

American (AMR)

AF:

0.219

AC:

9773

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2823

AN:

26122

East Asian (EAS)

AF:

0.198

AC:

7832

AN:

39646

South Asian (SAS)

AF:

0.170

AC:

14648

AN:

86230

European-Finnish (FIN)

AF:

0.210

AC:

11191

AN:

53406

Middle Eastern (MID)

AF:

0.165

AC:

951

AN:

5762

European-Non Finnish (NFE)

AF:

0.158

AC:

175898

AN:

1111018

Other (OTH)

AF:

0.168

AC:

10124

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

10322

20644

30966

41288

51610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6410

12820

19230

25640

32050

<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:

0.163

AC:

24777

AN:

152118

Hom.:

2159

Cov.:

AF XY:

0.167

AC XY:

12387

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.136

AC:

5628

AN:

41494

American (AMR)

AF:

0.199

AC:

3048

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3468

East Asian (EAS)

AF:

0.209

AC:

1083

AN:

5170

South Asian (SAS)

AF:

0.179

AC:

859

AN:

4804

European-Finnish (FIN)

AF:

0.208

AC:

2197

AN:

10580

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10946

AN:

67986

Other (OTH)

AF:

0.160

AC:

339

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1085

2170

3255

4340

5425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.153

Hom.:

3294

Bravo

AF:

0.161

Asia WGS

AF:

0.175

AC:

609

AN:

3478

EpiCase

AF:

0.155

EpiControl

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 20, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 05, 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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Congenital muscular dystrophy due to partial LAMA2 deficiency

Benign:1

Jan 12, 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

-0.56

CADD

Benign

8.4

(source)

DANN

Benign

0.62

PhyloP100

1.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over