rs1554301637
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PP3PP5_Moderate
The NM_000426.4(LAMA2):c.6993_7155del(p.Ser2331ArgfsTer5) variant causes a splice acceptor, coding sequence change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
LAMA2
NM_000426.4 splice_acceptor, coding_sequence
NM_000426.4 splice_acceptor, coding_sequence
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.48
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 6-129464288-AGTCCTCAGGTGGAAGATAGTGAGGGGACTATTCAATTTGATGGAGAAGGTTATGCATTGGTCAGCCGTCCCATTCGCTGGTACCCCAACATCTCCACTGTCATGTTCAAGTTCAGAACATTTTCTTCGAGTGCTCTTCTGATGTATCTTGCCACACGAGACCT-A is Pathogenic according to our data. Variant chr6-129464288-AGTCCTCAGGTGGAAGATAGTGAGGGGACTATTCAATTTGATGGAGAAGGTTATGCATTGGTCAGCCGTCCCATTCGCTGGTACCCCAACATCTCCACTGTCATGTTCAAGTTCAGAACATTTTCTTCGAGTGCTCTTCTGATGTATCTTGCCACACGAGACCT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 266109.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.6993_7155del | p.Ser2331ArgfsTer5 | splice_acceptor_variant, coding_sequence_variant | 50/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.6993_7155del | p.Ser2331ArgfsTer5 | splice_acceptor_variant, coding_sequence_variant | 50/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.6993_7155del | p.Ser2331ArgfsTer5 | splice_acceptor_variant, coding_sequence_variant | 50/65 | 5 | NM_000426.4 | ||
ENST00000665046.1 | n.976-23199_976-23037del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Merosin deficient congenital muscular dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS | Jan 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at