rs2297738

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.6237G>A(p.Thr2079Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,612,810 control chromosomes in the GnomAD database, including 21,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2159 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19787 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.70

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:

ENSG00000226149 (HGNC:):

ENSG00000226149 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 6-129440967-G-A is Benign according to our data. Variant chr6-129440967-G-A is described in ClinVar as [Benign]. Clinvar id is 92975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129440967-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 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.6237G>A	p.Thr2079Thr	synonymous_variant	43/65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.6237G>A	p.Thr2079Thr	synonymous_variant	43/64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAMA2	ENST00000421865.3 linkuse as main transcript	c.6237G>A	p.Thr2079Thr	synonymous_variant	43/65	5	NM_000426.4	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5 linkuse as main transcript	c.6501G>A	p.Thr2167Thr	synonymous_variant	44/66	5		ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5 linkuse as main transcript	c.6237G>A	p.Thr2079Thr	synonymous_variant	43/64	5		ENSP00000481744.2	A0A087WYF1
ENSG00000226149	ENST00000665046.1 linkuse as main transcript	n.1261C>T		non_coding_transcript_exon_variant	10/10

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24773

AN:

152000

Hom.:

2159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.208

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.163

GnomAD3 exomes

AF:

0.173

AC:

43412

AN:

250786

Hom.:

3973

AF XY:

0.171

AC XY:

23144

AN XY:

135544

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.220

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.217

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.214

Gnomad NFE exome

AF:

0.155

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.163

AC:

237679

AN:

1460692

Hom.:

19787

Cov.:

AF XY:

0.163

AC XY:

118245

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.219

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.198

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.158

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.163

AC:

24777

AN:

152118

Hom.:

2159

Cov.:

AF XY:

0.167

AC XY:

12387

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.208

Gnomad4 NFE

AF:

0.161

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.151

Hom.:

2370

Bravo

AF:

0.161

Asia WGS

AF:

0.175

AC:

609

AN:

3478

EpiCase

AF:

0.155

EpiControl

AF:

0.158

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 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	Eurofins Ntd Llc (ga)	Jan 20, 2016	- -

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 12, 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

-0.56

CADD

Benign

8.4

DANN

Benign

0.62

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