rs55776770

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000426.4(LAMA2):c.9212-15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,613,500 control chromosomes in the GnomAD database, including 946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 57 hom., cov: 33)

Exomes 𝑓: 0.032 ( 889 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.67

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:

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 6-129516175-C-A is Benign according to our data. Variant chr6-129516175-C-A is described in ClinVar as [Benign]. Clinvar id is 256095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129516175-C-A is described in Lovd as [Benign]. Variant chr6-129516175-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0227 (3454/152278) while in subpopulation NFE AF= 0.0365 (2480/68026). AF 95% confidence interval is 0.0353. There are 57 homozygotes in gnomad4. There are 1605 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.9212-15C>A		intron_variant		ENST00000421865.3	NP_000417.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 linkuse as main transcript	c.9212-15C>A		intron_variant		5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

3454

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00637

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0365

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0233

AC:

5860

AN:

251332

Hom.:

104

AF XY:

0.0231

AC XY:

3139

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00541

Gnomad AMR exome

AF:

0.0146

Gnomad ASJ exome

AF:

0.0387

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00346

Gnomad FIN exome

AF:

0.0230

Gnomad NFE exome

AF:

0.0363

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0324

AC:

47412

AN:

1461222

Hom.:

889

Cov.:

AF XY:

0.0313

AC XY:

22765

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00544

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.0369

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00390

Gnomad4 FIN exome

AF:

0.0247

Gnomad4 NFE exome

AF:

0.0379

Gnomad4 OTH exome

AF:

0.0285

GnomAD4 genome

AF:

0.0227

AC:

3454

AN:

152278

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1605

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00635

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.0365

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0198

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 13, 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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

LAMA2-related muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

- -

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

-0.82

CADD

Benign

0.22

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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