rs7754560

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000426.4(LAMA2):c.640-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,502,734 control chromosomes in the GnomAD database, including 33,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5257 hom., cov: 32)

Exomes 𝑓: 0.20 ( 28701 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.303

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-129143875-G-A is Benign according to our data. Variant chr6-129143875-G-A is described in ClinVar as Benign. ClinVar VariationId is 256079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.640-26G>A		intron_variant	Intron 4 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.640-26G>A		intron_variant	Intron 4 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 link	c.640-26G>A		intron_variant	Intron 4 of 64	5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.247

AC:

37442

AN:

151730

Hom.:

5257

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.193

AC:

45623

AN:

236086

AF XY:

0.196

show subpopulations

Gnomad AFR exome

AF:

0.380

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.178

Gnomad EAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.202

AC:

272252

AN:

1350886

Hom.:

28701

Cov.:

AF XY:

0.203

AC XY:

137054

AN XY:

676704

show subpopulations

African (AFR)

AF:

0.384

AC:

11582

AN:

30140

American (AMR)

AF:

0.123

AC:

5212

AN:

42508

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

4567

AN:

25054

East Asian (EAS)

AF:

0.143

AC:

5537

AN:

38826

South Asian (SAS)

AF:

0.240

AC:

19289

AN:

80354

European-Finnish (FIN)

AF:

0.202

AC:

10639

AN:

52634

Middle Eastern (MID)

AF:

0.240

AC:

1321

AN:

5498

European-Non Finnish (NFE)

AF:

0.198

AC:

202330

AN:

1019428

Other (OTH)

AF:

0.209

AC:

11775

AN:

56444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9365

18730

28094

37459

46824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6948

13896

20844

27792

34740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.247

AC:

37480

AN:

151848

Hom.:

5257

Cov.:

AF XY:

0.244

AC XY:

18108

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.391

AC:

16181

AN:

41392

American (AMR)

AF:

0.170

AC:

2587

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

660

AN:

3454

East Asian (EAS)

AF:

0.140

AC:

723

AN:

5158

South Asian (SAS)

AF:

0.247

AC:

1187

AN:

4812

European-Finnish (FIN)

AF:

0.204

AC:

2156

AN:

10556

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.197

AC:

13347

AN:

67916

Other (OTH)

AF:

0.232

AC:

489

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1406

2812

4219

5625

7031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.205

Hom.:

651

Bravo

AF:

0.249

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.6

(source)

DANN

Benign

0.61

PhyloP100

0.30

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over