rs3798663

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000426.4(LAMA2):c.3411+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,520,938 control chromosomes in the GnomAD database, including 30,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6769 hom., cov: 33)

Exomes 𝑓: 0.16 ( 23802 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.05

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-129313110-G-A is Benign according to our data. Variant chr6-129313110-G-A is described in ClinVar as [Benign]. Clinvar id is 92951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129313110-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 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.3411+13G>A		intron_variant		ENST00000421865.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.3411+13G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
LAMA2	ENST00000421865.3 linkuse as main transcript	c.3411+13G>A	intron_variant	5	NM_000426.4
LAMA2	ENST00000617695.5 linkuse as main transcript	c.3411+13G>A	intron_variant	5
LAMA2	ENST00000618192.5 linkuse as main transcript	c.3675+13G>A	intron_variant	5		P1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38619

AN:

151972

Hom.:

6752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.222

AC:

52098

AN:

234696

Hom.:

8160

AF XY:

0.209

AC XY:

26382

AN XY:

126370

show subpopulations

Gnomad AFR exome

AF:

0.463

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.552

Gnomad SAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.122

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.162

AC:

221945

AN:

1368848

Hom.:

23802

Cov.:

AF XY:

0.161

AC XY:

109445

AN XY:

679364

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.334

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.547

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.254

AC:

38680

AN:

152090

Hom.:

6769

Cov.:

AF XY:

0.258

AC XY:

19201

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.461

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.544

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.148

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.206

Hom.:

1119

Bravo

AF:

0.280

Asia WGS

AF:

0.307

AC:

1069

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 20, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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	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. -

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

-0.82

CADD

Benign

0.22

DANN

Benign

0.56

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