Genetic Variant LAMA2:c.113-68783T>C (chr6-128981135-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000426.4(LAMA2):c.113-68783T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,052 control chromosomes in the GnomAD database, including 3,450 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 3450 hom., cov: 31)

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.157

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

congenital merosin-deficient muscular dystrophy 1A
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
LAMA2-related muscular dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
muscular dystrophy, limb-girdle, autosomal recessive 23
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LAMA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.113-68783T>C		intron_variant	Intron 1 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.113-68783T>C		intron_variant	Intron 1 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 link	c.113-68783T>C		intron_variant	Intron 1 of 64	5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23249

AN:

151932

Hom.:

3447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.0473

Gnomad AMR

AF:

0.0901

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.0459

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.0576

Gnomad OTH

AF:

0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.153

AC:

23299

AN:

152052

Hom.:

3450

Cov.:

AF XY:

0.151

AC XY:

11212

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.386

AC:

15967

AN:

41394

American (AMR)

AF:

0.0900

AC:

1376

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

390

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5160

South Asian (SAS)

AF:

0.159

AC:

764

AN:

4818

European-Finnish (FIN)

AF:

0.0459

AC:

487

AN:

10604

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0576

AC:

3916

AN:

68006

Other (OTH)

AF:

0.145

AC:

306

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

811

1622

2432

3243

4054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0864

Hom.:

1487

Bravo

AF:

0.164

Asia WGS

AF:

0.0980

AC:

343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.1

(source)

DANN

Benign

0.38

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over