Variant 6-129454325-T-C 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.6707+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,558,298 control chromosomes in the GnomAD database, including 15,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1656 hom., cov: 32)

Exomes 𝑓: 0.14 ( 13707 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.08

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-129454325-T-C is Benign according to our data. Variant chr6-129454325-T-C is described in ClinVar as [Benign]. Clinvar id is 256083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129454325-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.6707+37T>C		intron_variant		ENST00000421865.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.6707+37T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3 linkuse as main transcript	c.6707+37T>C		intron_variant		5	NM_000426.4
	ENST00000665046.1 linkuse as main transcript	n.976-13073A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21723

AN:

152014

Hom.:

1658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.157

AC:

36107

AN:

229938

Hom.:

2935

AF XY:

0.153

AC XY:

19086

AN XY:

124380

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.0989

Gnomad EAS exome

AF:

0.226

Gnomad SAS exome

AF:

0.157

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.136

AC:

191826

AN:

1406166

Hom.:

13707

Cov.:

AF XY:

0.137

AC XY:

95924

AN XY:

701884

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.212

Gnomad4 ASJ exome

AF:

0.0949

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.153

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.144

GnomAD4 genome

AF:

0.143

AC:

21727

AN:

152132

Hom.:

1656

Cov.:

AF XY:

0.144

AC XY:

10729

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.211

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.130

Hom.:

240

Bravo

AF:

0.145

Asia WGS

AF:

0.163

AC:

568

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.2

DANN

Benign

0.58

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