rs748257607
Positions:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate
The NM_000426.4(LAMA2):c.3977G>A(p.Arg1326Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000373 in 1,610,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
LAMA2
NM_000426.4 missense
NM_000426.4 missense
Scores
2
5
6
Clinical Significance
Conservation
PhyloP100: 4.45
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 Likely_benign. Variant got -2 ACMG points.
BP6
?
Variant 6-129316090-G-A is Benign according to our data. Variant chr6-129316090-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 477466.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.3977G>A | p.Arg1326Gln | missense_variant | 27/65 | ENST00000421865.3 | |
LAMA2 | NM_001079823.2 | c.3977G>A | p.Arg1326Gln | missense_variant | 27/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMA2 | ENST00000421865.3 | c.3977G>A | p.Arg1326Gln | missense_variant | 27/65 | 5 | NM_000426.4 | ||
LAMA2 | ENST00000618192.5 | c.4241G>A | p.Arg1414Gln | missense_variant | 28/66 | 5 | P1 | ||
LAMA2 | ENST00000617695.5 | c.3977G>A | p.Arg1326Gln | missense_variant | 27/64 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152146Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251230Hom.: 1 AF XY: 0.0000221 AC XY: 3AN XY: 135802
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GnomAD4 exome AF: 0.0000329 AC: 48AN: 1458054Hom.: 0 Cov.: 30 AF XY: 0.0000358 AC XY: 26AN XY: 725634
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GnomAD4 genome ? AF: 0.0000789 AC: 12AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74324
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
LAMA2-related muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
1.0
.;.;D
Vest4
MutPred
Loss of phosphorylation at T1323 (P = 0.1045);Loss of phosphorylation at T1323 (P = 0.1045);Loss of phosphorylation at T1323 (P = 0.1045);
MVP
MPC
0.23
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at