rs3749878

Positions:

Variant summary

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

The NM_000426.4(LAMA2):c.5502G>A(p.Glu1834=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,600,776 control chromosomes in the GnomAD database, including 183,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20023 hom., cov: 32)

Exomes 𝑓: 0.47 ( 163053 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.662

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=-0.71).

BP6

Variant 6-129401280-G-A is Benign according to our data. Variant chr6-129401280-G-A is described in ClinVar as [Benign]. Clinvar id is 92967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129401280-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.662 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.5502G>A	p.Glu1834=	synonymous_variant	38/65	ENST00000421865.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.5502G>A	p.Glu1834=	synonymous_variant	38/64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LAMA2	ENST00000421865.3 linkuse as main transcript	c.5502G>A	p.Glu1834=	synonymous_variant	38/65	5	NM_000426.4
LAMA2	ENST00000618192.5 linkuse as main transcript	c.5766G>A	p.Glu1922=	synonymous_variant	39/66	5		P1
LAMA2	ENST00000617695.5 linkuse as main transcript	c.5502G>A	p.Glu1834=	synonymous_variant	38/64	5

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

76955

AN:

151890

Hom.:

19980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.619

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.496

GnomAD3 exomes

AF:

0.493

AC:

123635

AN:

250918

Hom.:

30994

AF XY:

0.492

AC XY:

66691

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.622

Gnomad AMR exome

AF:

0.472

Gnomad ASJ exome

AF:

0.540

Gnomad EAS exome

AF:

0.572

Gnomad SAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.459

Gnomad OTH exome

AF:

0.481

GnomAD4 exome

AF:

0.470

AC:

681074

AN:

1448768

Hom.:

163053

Cov.:

AF XY:

0.471

AC XY:

340054

AN XY:

721386

show subpopulations

Gnomad4 AFR exome

AF:

0.633

Gnomad4 AMR exome

AF:

0.475

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.533

Gnomad4 SAS exome

AF:

0.542

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.455

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

AF:

0.507

AC:

77068

AN:

152008

Hom.:

20023

Cov.:

AF XY:

0.508

AC XY:

37718

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.619

Gnomad4 AMR

AF:

0.462

Gnomad4 ASJ

AF:

0.522

Gnomad4 EAS

AF:

0.551

Gnomad4 SAS

AF:

0.534

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.494

Alfa

AF:

0.469

Hom.:

31641

Bravo

AF:

0.513

Asia WGS

AF:

0.512

AC:

1783

AN:

3478

EpiCase

AF:

0.460

EpiControl

AF:

0.463

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 18, 2012	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Merosin deficient congenital muscular dystrophy

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

LAMA2-related muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Congenital muscular dystrophy due to partial LAMA2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.7

DANN

Benign

0.90

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