Variant rs3828735 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000426.4(LAMA2):c.5727-24T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,594,536 control chromosomes in the GnomAD database, including 176,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19480 hom., cov: 32)

Exomes 𝑓: 0.46 ( 157112 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.28

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=-0.77).

BP6

Variant 6-129403797-T-A is Benign according to our data. Variant chr6-129403797-T-A is described in ClinVar as [Benign]. Clinvar id is 256076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129403797-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.5727-24T>A		intron_variant		ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.5727-24T>A		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LAMA2	ENST00000421865.3 link	c.5727-24T>A	intron_variant	5	NM_000426.4	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5 link	c.5991-24T>A	intron_variant	5		ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5 link	c.5727-24T>A	intron_variant	5		ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes

AF:

0.501

AC:

75842

AN:

151470

Hom.:

19436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.474

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.493

GnomAD3 exomes

AF:

0.485

AC:

121078

AN:

249442

Hom.:

29699

AF XY:

0.485

AC XY:

65385

AN XY:

134938

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.567

Gnomad SAS exome

AF:

0.536

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.462

AC:

667086

AN:

1442946

Hom.:

157112

Cov.:

AF XY:

0.464

AC XY:

333496

AN XY:

718816

show subpopulations

Gnomad4 AFR exome

AF:

0.630

Gnomad4 AMR exome

AF:

0.473

Gnomad4 ASJ exome

AF:

0.530

Gnomad4 EAS exome

AF:

0.531

Gnomad4 SAS exome

AF:

0.539

Gnomad4 FIN exome

AF:

0.457

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.501

AC:

75955

AN:

151590

Hom.:

19480

Cov.:

AF XY:

0.501

AC XY:

37119

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.616

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.547

Gnomad4 SAS

AF:

0.529

Gnomad4 FIN

AF:

0.438

Gnomad4 NFE

AF:

0.445

Gnomad4 OTH

AF:

0.491

Alfa

AF:

0.395

Hom.:

1773

Bravo

AF:

0.509

Asia WGS

AF:

0.510

AC:

1775

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Merosin deficient congenital muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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. -

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

-0.77

CADD

Benign

3.5

DANN

Benign

0.74

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