rs2229850

Variant summary

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

The NM_000426.4(LAMA2):c.7845G>A(p.Pro2615=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,613,270 control chromosomes in the GnomAD database, including 67,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10420 hom., cov: 32)

Exomes 𝑓: 0.27 ( 57191 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.698

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:

(HGNC:):

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=-0.61).

BP6

Variant 6-129486569-G-A is Benign according to our data. Variant chr6-129486569-G-A is described in ClinVar as [Benign]. Clinvar id is 92988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129486569-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.698 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 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.7845G>A	p.Pro2615=	synonymous_variant	56/65	ENST00000421865.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.7833G>A	p.Pro2611=	synonymous_variant	55/64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3 linkuse as main transcript	c.7845G>A	p.Pro2615=	synonymous_variant	56/65	5	NM_000426.4
	ENST00000665046.1 linkuse as main transcript	n.975+16036C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

53024

AN:

151958

Hom.:

10404

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.212

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.304

AC:

76308

AN:

251054

Hom.:

12308

AF XY:

0.298

AC XY:

40377

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.546

Gnomad AMR exome

AF:

0.306

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.394

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.259

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.274

AC:

400241

AN:

1461194

Hom.:

57191

Cov.:

AF XY:

0.274

AC XY:

199329

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.549

Gnomad4 AMR exome

AF:

0.305

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.372

Gnomad4 SAS exome

AF:

0.308

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.257

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.349

AC:

53077

AN:

152076

Hom.:

10420

Cov.:

AF XY:

0.350

AC XY:

25989

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.539

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.212

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.285

Hom.:

4680

Bravo

AF:

0.359

Asia WGS

AF:

0.348

AC:

1211

AN:

3478

EpiCase

AF:

0.250

EpiControl

AF:

0.248

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

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 26, 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	Eurofins Ntd Llc (ga)	Jan 20, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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	-	- -

Merosin deficient congenital muscular dystrophy

Benign:2

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

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

-0.61

Cadd

Benign

6.6

Dann

Benign

0.85

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