rs2306220

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.1491T>C(p.Cys497Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 1,613,580 control chromosomes in the GnomAD database, including 1,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 101 hom., cov: 32)

Exomes 𝑓: 0.020 ( 1036 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.301

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:

LAMA2 (HGNC:):

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=-0.53).

BP6

Variant 6-129190228-T-C is Benign according to our data. Variant chr6-129190228-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 129433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129190228-T-C is described in Lovd as [Benign]. Variant chr6-129190228-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.301 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.1491T>C	p.Cys497Cys	synonymous_variant	11/65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.1491T>C	p.Cys497Cys	synonymous_variant	11/64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 linkuse as main transcript	c.1491T>C	p.Cys497Cys	synonymous_variant	11/65	5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3219

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.0811

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0319

AC:

8000

AN:

251138

Hom.:

340

AF XY:

0.0341

AC XY:

4625

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.0683

Gnomad FIN exome

AF:

0.0224

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0202

AC:

29569

AN:

1461270

Hom.:

1036

Cov.:

AF XY:

0.0218

AC XY:

15883

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.0209

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.0679

Gnomad4 FIN exome

AF:

0.0225

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0212

AC:

3232

AN:

152310

Hom.:

101

Cov.:

AF XY:

0.0234

AC XY:

1745

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0156

Gnomad4 AMR

AF:

0.0170

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.0804

Gnomad4 FIN

AF:

0.0219

Gnomad4 NFE

AF:

0.0112

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0200

Asia WGS

AF:

0.114

AC:

395

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0121

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 15, 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. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

LAMA2-related muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.5

DANN

Benign

0.64

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