chr6-129049961-C-T

Position:

chr6-129049961-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000426.4(LAMA2):c.156C>T(p.Ile52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,378 control chromosomes in the GnomAD database, including 9,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 708 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8512 hom. )

Consequence

LAMA2
NM_000426.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.47

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 6-129049961-C-T is Benign according to our data. Variant chr6-129049961-C-T is described in ClinVar as [Benign]. Clinvar id is 92938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129049961-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.156C>T	p.Ile52=	synonymous_variant	2/65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.156C>T	p.Ile52=	synonymous_variant	2/64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 linkuse as main transcript	c.156C>T	p.Ile52=	synonymous_variant	2/65	5	NM_000426.4	ENSP00000400365

Frequencies

GnomAD3 genomes

AF:

0.0847

AC:

12879

AN:

152030

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0182

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.0549

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0917

GnomAD3 exomes

AF:

0.0985

AC:

24764

AN:

251472

Hom.:

1415

AF XY:

0.101

AC XY:

13686

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.0649

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.0551

Gnomad FIN exome

AF:

0.0953

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.104

AC:

151994

AN:

1461230

Hom.:

8512

Cov.:

AF XY:

0.104

AC XY:

75563

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.0669

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.0580

Gnomad4 FIN exome

AF:

0.0957

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0847

AC:

12883

AN:

152148

Hom.:

708

Cov.:

AF XY:

0.0829

AC XY:

6165

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.0809

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.0552

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.0931

Alfa

AF:

0.104

Hom.:

1016

Bravo

AF:

0.0827

Asia WGS

AF:

0.107

AC:

372

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 08, 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	Eurofins Ntd Llc (ga)	Sep 20, 2012	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Merosin deficient congenital muscular dystrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 13, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

LAMA2-related muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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. -

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

-0.30

CADD

Benign

9.3

DANN

Benign

0.81

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