6-129369987-C-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.4956C>G(p.Thr1652Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 1,613,146 control chromosomes in the GnomAD database, including 4,638 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. T1652T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.081 ( 612 hom., cov: 32)

Exomes 𝑓: 0.065 ( 4026 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.45

Publications

11 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=-0.51).

BP6

Variant 6-129369987-C-G is Benign according to our data. Variant chr6-129369987-C-G is described in ClinVar as Benign. ClinVar VariationId is 92963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.135 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.4956C>G	p.Thr1652Thr	synonymous	Exon 34 of 65	NP_000417.3
	LAMA2	NM_001079823.2		c.4956C>G	p.Thr1652Thr	synonymous	Exon 34 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.4956C>G	p.Thr1652Thr	synonymous	Exon 34 of 65	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5	TSL:5	c.5220C>G	p.Thr1740Thr	synonymous	Exon 35 of 66	ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5	TSL:5	c.4956C>G	p.Thr1652Thr	synonymous	Exon 34 of 64	ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes

AF:

0.0812

AC:

12345

AN:

152054

Hom.:

608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.0850

Gnomad EAS

AF:

0.0350

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0517

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0572

Gnomad OTH

AF:

0.0934

GnomAD2 exomes

AF:

0.0887

AC:

22204

AN:

250462

AF XY:

0.0879

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.0845

Gnomad EAS exome

AF:

0.0305

Gnomad FIN exome

AF:

0.0487

Gnomad NFE exome

AF:

0.0604

Gnomad OTH exome

AF:

0.0876

GnomAD4 exome

AF:

0.0651

AC:

95146

AN:

1460974

Hom.:

4026

Cov.:

AF XY:

0.0669

AC XY:

48639

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.112

AC:

3740

AN:

33436

American (AMR)

AF:

0.185

AC:

8252

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0880

AC:

2298

AN:

26126

East Asian (EAS)

AF:

0.0298

AC:

1183

AN:

39684

South Asian (SAS)

AF:

0.131

AC:

11294

AN:

86216

European-Finnish (FIN)

AF:

0.0502

AC:

2681

AN:

53386

Middle Eastern (MID)

AF:

0.116

AC:

666

AN:

5766

European-Non Finnish (NFE)

AF:

0.0543

AC:

60376

AN:

1111290

Other (OTH)

AF:

0.0771

AC:

4656

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4318

8636

12954

17272

21590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2354

4708

7062

9416

11770

<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:

0.0813

AC:

12373

AN:

152172

Hom.:

612

Cov.:

AF XY:

0.0824

AC XY:

6126

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.109

AC:

4507

AN:

41512

American (AMR)

AF:

0.140

AC:

2138

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0850

AC:

295

AN:

3470

East Asian (EAS)

AF:

0.0349

AC:

181

AN:

5182

South Asian (SAS)

AF:

0.119

AC:

575

AN:

4818

European-Finnish (FIN)

AF:

0.0517

AC:

548

AN:

10592

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0572

AC:

3891

AN:

68010

Other (OTH)

AF:

0.0943

AC:

199

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

594

1187

1781

2374

2968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0678

Hom.:

133

Bravo

AF:

0.0884

Asia WGS

AF:

0.108

AC:

362

AN:

3372

EpiCase

AF:

0.0634

EpiControl

AF:

0.0691

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Congenital muscular dystrophy due to partial LAMA2 deficiency (1)

LAMA2-related muscular dystrophy (1)

Merosin deficient congenital muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.0

(source)

DANN

Benign

0.56

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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