6-129260736-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000426.4(LAMA2):​c.2122G>T​(p.Ala708Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,456 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LAMA2
NM_000426.4 missense

Scores

2
5
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.34
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMA2NM_000426.4 linkc.2122G>T p.Ala708Ser missense_variant Exon 15 of 65 ENST00000421865.3 NP_000417.3
LAMA2NM_001079823.2 linkc.2122G>T p.Ala708Ser missense_variant Exon 15 of 64 NP_001073291.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMA2ENST00000421865.3 linkc.2122G>T p.Ala708Ser missense_variant Exon 15 of 65 5 NM_000426.4 ENSP00000400365.2 P24043
LAMA2ENST00000618192.5 linkc.2122G>T p.Ala708Ser missense_variant Exon 15 of 66 5 ENSP00000480802.2 A0A087WX80
LAMA2ENST00000617695.5 linkc.2122G>T p.Ala708Ser missense_variant Exon 15 of 64 5 ENSP00000481744.2 A0A087WYF1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459456
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.034
.;T;T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.051
D
MetaRNN
Uncertain
0.74
D;D;D
MetaSVM
Benign
-0.61
T
MutationAssessor
Pathogenic
3.0
.;.;M
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-2.1
.;.;N
REVEL
Uncertain
0.30
Sift
Benign
0.10
.;.;T
Polyphen
0.85
.;.;P
Vest4
0.63
MVP
0.71
MPC
0.45
ClinPred
0.90
D
GERP RS
4.7
Varity_R
0.22
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777765933; hg19: chr6-129581881; API