rs757404275
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000426.4(LAMA2):c.6919_6920delTA(p.Tyr2307LeufsTer2) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,459,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
LAMA2
NM_000426.4 frameshift
NM_000426.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.96
Publications
0 publications found
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 1AInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
- LAMA2-related muscular dystrophyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- muscular dystrophy, limb-girdle, autosomal recessive 23Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-129460249-CAT-C is Pathogenic according to our data. Variant chr6-129460249-CAT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 550950.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000426.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LAMA2 | NM_000426.4 | MANE Select | c.6919_6920delTA | p.Tyr2307LeufsTer2 | frameshift | Exon 49 of 65 | NP_000417.3 | ||
| LAMA2 | NM_001079823.2 | c.6919_6920delTA | p.Tyr2307LeufsTer2 | frameshift | Exon 49 of 64 | NP_001073291.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LAMA2 | ENST00000421865.3 | TSL:5 MANE Select | c.6919_6920delTA | p.Tyr2307LeufsTer2 | frameshift | Exon 49 of 65 | ENSP00000400365.2 | ||
| LAMA2 | ENST00000618192.5 | TSL:5 | c.7183_7184delTA | p.Tyr2395LeufsTer2 | frameshift | Exon 50 of 66 | ENSP00000480802.2 | ||
| LAMA2 | ENST00000617695.5 | TSL:5 | c.6919_6920delTA | p.Tyr2307LeufsTer2 | frameshift | Exon 49 of 64 | ENSP00000481744.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000399 AC: 1AN: 250658 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
250658
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459702Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 726270 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1459702
Hom.:
AF XY:
AC XY:
0
AN XY:
726270
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33382
American (AMR)
AF:
AC:
0
AN:
44630
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26058
East Asian (EAS)
AF:
AC:
0
AN:
39654
South Asian (SAS)
AF:
AC:
0
AN:
86216
European-Finnish (FIN)
AF:
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1110350
Other (OTH)
AF:
AC:
0
AN:
60258
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
LAMA2-related muscular dystrophy (1)
1
-
-
Merosin deficient congenital muscular dystrophy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
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.