rs376693904
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000426.4(LAMA2):c.5280G>A(p.Glu1760=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,614,018 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00033 ( 6 hom. )
Consequence
LAMA2
NM_000426.4 synonymous
NM_000426.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.194
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 6-129393090-G-A is Benign according to our data. Variant chr6-129393090-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129393090-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.194 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000332 (485/1461722) while in subpopulation SAS AF= 0.00449 (387/86256). AF 95% confidence interval is 0.00412. There are 6 homozygotes in gnomad4_exome. There are 333 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 6 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMA2 | NM_000426.4 | c.5280G>A | p.Glu1760= | synonymous_variant | 37/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.5280G>A | p.Glu1760= | synonymous_variant | 37/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.5280G>A | p.Glu1760= | synonymous_variant | 37/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.5544G>A | p.Glu1848= | synonymous_variant | 38/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.5280G>A | p.Glu1760= | synonymous_variant | 37/64 | 5 | |||
LAMA2 | ENST00000687590.1 | n.1700G>A | non_coding_transcript_exon_variant | 5/5 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
16
AN:
152178
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000638 AC: 160AN: 250594Hom.: 0 AF XY: 0.000871 AC XY: 118AN XY: 135550
GnomAD3 exomes
AF:
AC:
160
AN:
250594
Hom.:
AF XY:
AC XY:
118
AN XY:
135550
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000332 AC: 485AN: 1461722Hom.: 6 Cov.: 31 AF XY: 0.000458 AC XY: 333AN XY: 727154
GnomAD4 exome
AF:
AC:
485
AN:
1461722
Hom.:
Cov.:
31
AF XY:
AC XY:
333
AN XY:
727154
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74470
GnomAD4 genome
?
AF:
AC:
16
AN:
152296
Hom.:
Cov.:
32
AF XY:
AC XY:
9
AN XY:
74470
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
LAMA2-related muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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