6-129049961-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000426.4(LAMA2):c.156C>T(p.Ile52Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,378 control chromosomes in the GnomAD database, including 9,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 708 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8512 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.47

Publications

17 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 6-129049961-C-T is Benign according to our data. Variant chr6-129049961-C-T is described in ClinVar as [Benign]. Clinvar id is 92938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.156C>T	p.Ile52Ile	synonymous_variant	Exon 2 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.156C>T	p.Ile52Ile	synonymous_variant	Exon 2 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 link	c.156C>T	p.Ile52Ile	synonymous_variant	Exon 2 of 65	5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.0847

AC:

12879

AN:

152030

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.0549

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0917

GnomAD2 exomes

AF:

0.0985

AC:

24764

AN:

251472

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.0649

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.0953

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.104

AC:

151994

AN:

1461230

Hom.:

8512

Cov.:

AF XY:

0.104

AC XY:

75563

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.0173

AC:

580

AN:

33472

American (AMR)

AF:

0.0669

AC:

2992

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4714

AN:

26132

East Asian (EAS)

AF:

0.170

AC:

6736

AN:

39692

South Asian (SAS)

AF:

0.0580

AC:

5005

AN:

86238

European-Finnish (FIN)

AF:

0.0957

AC:

5114

AN:

53414

Middle Eastern (MID)

AF:

0.135

AC:

779

AN:

5768

European-Non Finnish (NFE)

AF:

0.108

AC:

119840

AN:

1111422

Other (OTH)

AF:

0.103

AC:

6234

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6992

13985

20977

27970

34962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0847

AC:

12883

AN:

152148

Hom.:

708

Cov.:

AF XY:

0.0829

AC XY:

6165

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0181

AC:

752

AN:

41538

American (AMR)

AF:

0.0809

AC:

1237

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

591

AN:

3466

East Asian (EAS)

AF:

0.155

AC:

799

AN:

5160

South Asian (SAS)

AF:

0.0552

AC:

266

AN:

4822

European-Finnish (FIN)

AF:

0.103

AC:

1092

AN:

10562

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.114

AC:

7782

AN:

67996

Other (OTH)

AF:

0.0931

AC:

196

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

594

1188

1781

2375

2969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.103

Hom.:

1237

Bravo

AF:

0.0827

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 08, 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. -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 20, 2012

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

- -

Merosin deficient congenital muscular dystrophy

Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 13, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

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 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. -

Muscular dystrophy, limb-girdle, autosomal recessive 23

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.3

(source)

DANN

Benign

0.81

PhyloP100

1.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-129049961-C-T

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