6-129349403-C-T

Variant names:

Variant summary

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

The NM_000426.4(LAMA2):c.4523+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 1,573,726 control chromosomes in the GnomAD database, including 4,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 633 hom., cov: 32)

Exomes 𝑓: 0.066 ( 4013 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.418

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=-0.83).

BP6

Variant 6-129349403-C-T is Benign according to our data. Variant chr6-129349403-C-T is described in ClinVar as [Benign]. Clinvar id is 92960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129349403-C-T is described in Lovd as [Benign]. Variant chr6-129349403-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.4523+19C>T		intron_variant	Intron 31 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.4523+19C>T		intron_variant	Intron 31 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 link	c.4523+19C>T		intron_variant	Intron 31 of 64	5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.0827

AC:

12563

AN:

151828

Hom.:

629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.0849

Gnomad EAS

AF:

0.0355

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0526

Gnomad MID

AF:

0.0924

Gnomad NFE

AF:

0.0577

Gnomad OTH

AF:

0.0954

GnomAD3 exomes

AF:

0.0891

AC:

22382

AN:

251162

Hom.:

1408

AF XY:

0.0884

AC XY:

11993

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.189

Gnomad ASJ exome

AF:

0.0847

Gnomad EAS exome

AF:

0.0313

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.0492

Gnomad NFE exome

AF:

0.0607

Gnomad OTH exome

AF:

0.0882

GnomAD4 exome

AF:

0.0659

AC:

93730

AN:

1421780

Hom.:

4013

Cov.:

AF XY:

0.0678

AC XY:

48130

AN XY:

709810

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.0883

Gnomad4 EAS exome

AF:

0.0304

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.0509

Gnomad4 NFE exome

AF:

0.0548

Gnomad4 OTH exome

AF:

0.0780

GnomAD4 genome

AF:

0.0829

AC:

12591

AN:

151946

Hom.:

633

Cov.:

AF XY:

0.0838

AC XY:

6225

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.142

Gnomad4 ASJ

AF:

0.0849

Gnomad4 EAS

AF:

0.0353

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0526

Gnomad4 NFE

AF:

0.0576

Gnomad4 OTH

AF:

0.0963

Alfa

AF:

0.0724

Hom.:

624

Bravo

AF:

0.0900

Asia WGS

AF:

0.105

AC:

365

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Sep 21, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Merosin deficient congenital muscular dystrophy

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

LAMA2-related muscular dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Clinical Genetics, Academic Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.17

DANN

Benign

0.60

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