Genetic Variant LAMA2:c.112+29974G>T (chr6-128913331-G-T) – 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.112+29974G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,144 control chromosomes in the GnomAD database, including 550 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 0.040 ( 550 hom., cov: 32)

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.323

Publications

2 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.112+29974G>T		intron_variant	Intron 1 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.112+29974G>T		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.112+29974G>T		intron_variant	Intron 1 of 64	5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6118

AN:

152024

Hom.:

548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00918

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0483

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

GnomAD4 genome

AF:

0.0402

AC:

6117

AN:

152144

Hom.:

550

Cov.:

AF XY:

0.0442

AC XY:

3290

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00915

AC:

380

AN:

41528

American (AMR)

AF:

0.145

AC:

2216

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

144

AN:

3472

East Asian (EAS)

AF:

0.345

AC:

1777

AN:

5156

South Asian (SAS)

AF:

0.0416

AC:

201

AN:

4828

European-Finnish (FIN)

AF:

0.0129

AC:

136

AN:

10580

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0170

AC:

1159

AN:

68000

Other (OTH)

AF:

0.0478

AC:

101

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

260

519

779

1038

1298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0323

Hom.:

679

Bravo

AF:

0.0510

Asia WGS

AF:

0.174

AC:

603

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.1

(source)

DANN

Benign

0.70

PhyloP100

0.32

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