Variant rs369558532 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_000426.4(LAMA2):c.7440-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,488,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

LAMA2
NM_000426.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003055

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.317

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-129475381-G-A is Benign according to our data. Variant chr6-129475381-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 197945.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.7440-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000421865.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.7439+2029G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
LAMA2	ENST00000421865.3 linkuse as main transcript	c.7440-9G>A	splice_polypyrimidine_tract_variant, intron_variant	5	NM_000426.4
	ENST00000665046.1 linkuse as main transcript	n.975+27224C>T	intron_variant, non_coding_transcript_variant
LAMA2	ENST00000617695.5 linkuse as main transcript	c.7439+2029G>A	intron_variant	5
LAMA2	ENST00000618192.5 linkuse as main transcript	c.7704-9G>A	splice_polypyrimidine_tract_variant, intron_variant	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000523

AC:

AN:

143408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000201

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000756

Gnomad OTH

AF:

0.000523

GnomAD3 exomes

AF:

0.000165

AC:

AN:

236158

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

127804

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000172

Gnomad SAS exome

AF:

0.0000696

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000466

Gnomad OTH exome

AF:

0.000346

GnomAD4 exome

AF:

0.000114

AC:

153

AN:

1345394

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

672756

show subpopulations

Gnomad4 AFR exome

AF:

0.00184

Gnomad4 AMR exome

AF:

0.0000459

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000104

Gnomad4 SAS exome

AF:

0.0000640

Gnomad4 FIN exome

AF:

0.0000634

Gnomad4 NFE exome

AF:

0.0000706

Gnomad4 OTH exome

AF:

0.000178

GnomAD4 genome

AF:

0.000523

AC:

AN:

143516

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

AN XY:

69380

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000201

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000757

Gnomad4 OTH

AF:

0.000517

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.000465

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 20, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 2021	- -

LAMA2-related muscular dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.5

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.10

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