dbSNP rs6940025: LAMA2:c.1306+881T>A (chr6-129166556-T-A) – 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.1306+881T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 152,232 control chromosomes in the GnomAD database, including 675 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 0.068 ( 675 hom., cov: 32)

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.495

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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.1306+881T>A		intron_variant	Intron 9 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.1306+881T>A		intron_variant	Intron 9 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 link	c.1306+881T>A		intron_variant	Intron 9 of 64	5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes

AF:

0.0683

AC:

10395

AN:

152114

Hom.:

673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0383

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.0252

Gnomad SAS

AF:

0.0693

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0291

Gnomad OTH

AF:

0.0573

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

GnomAD4 genome

AF:

0.0684

AC:

10420

AN:

152232

Hom.:

675

Cov.:

AF XY:

0.0668

AC XY:

4975

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.170

AC:

7072

AN:

41510

American (AMR)

AF:

0.0383

AC:

585

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3470

East Asian (EAS)

AF:

0.0249

AC:

129

AN:

5186

South Asian (SAS)

AF:

0.0700

AC:

338

AN:

4828

European-Finnish (FIN)

AF:

0.0101

AC:

107

AN:

10614

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0291

AC:

1976

AN:

68018

Other (OTH)

AF:

0.0562

AC:

119

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

474

948

1421

1895

2369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0511

Hom.:

Bravo

AF:

0.0761

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.1

(source)

DANN

Benign

0.46

PhyloP100

0.49

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