6-129291663-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000426.4(LAMA2):c.2799A>G(p.Gln933Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,612,996 control chromosomes in the GnomAD database, including 52,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5756 hom., cov: 33)

Exomes 𝑓: 0.25 ( 46534 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.04

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 6-129291663-A-G is Benign according to our data. Variant chr6-129291663-A-G is described in ClinVar as [Benign]. Clinvar id is 92949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129291663-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.2799A>G	p.Gln933Gln	synonymous_variant	Exon 20 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.2799A>G	p.Gln933Gln	synonymous_variant	Exon 20 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA2	ENST00000421865.3 link	c.2799A>G	p.Gln933Gln	synonymous_variant	Exon 20 of 65	5	NM_000426.4	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5 link	c.2799A>G	p.Gln933Gln	synonymous_variant	Exon 20 of 66	5		ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5 link	c.2799A>G	p.Gln933Gln	synonymous_variant	Exon 20 of 64	5		ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40759

AN:

152006

Hom.:

5749

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.270

AC:

67795

AN:

251332

Hom.:

9653

AF XY:

0.269

AC XY:

36477

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.270

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.435

Gnomad SAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.246

AC:

359857

AN:

1460872

Hom.:

46534

Cov.:

AF XY:

0.248

AC XY:

180095

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.284

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.268

AC:

40787

AN:

152124

Hom.:

5756

Cov.:

AF XY:

0.271

AC XY:

20144

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.234

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.455

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.217

Hom.:

1962

Bravo

AF:

0.270

Asia WGS

AF:

0.344

AC:

1196

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.230

ClinVar

Significance: Benign

Submissions summary: Benign:12

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

- -

Jul 10, 2012

Eurofins Ntd Llc (ga)

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. -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

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

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Merosin deficient congenital muscular dystrophy

Benign:3

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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 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

-0.85

CADD

Benign

0.53

DANN

Benign

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over