20-62322431-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_005560.6(LAMA5):c.6184G>C(p.Asp2062His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2062N) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
LAMA5
NM_005560.6 missense
NM_005560.6 missense
Scores
1
2
16
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.15
Publications
0 publications found
Genes affected
LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]
LAMA5 Gene-Disease associations (from GenCC):
- nephrotic syndrome, IIa 26Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- LAMA5-related multisystemic syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.794
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151924Hom.: 0 Cov.: 34 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151924
Hom.:
Cov.:
34
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:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000139 AC: 2AN: 1435904Hom.: 0 Cov.: 61 AF XY: 0.00000140 AC XY: 1AN XY: 712290 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
2
AN:
1435904
Hom.:
Cov.:
61
AF XY:
AC XY:
1
AN XY:
712290
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33094
American (AMR)
AF:
AC:
0
AN:
41134
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25528
East Asian (EAS)
AF:
AC:
0
AN:
38406
South Asian (SAS)
AF:
AC:
0
AN:
83088
European-Finnish (FIN)
AF:
AC:
0
AN:
49850
Middle Eastern (MID)
AF:
AC:
0
AN:
5714
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1099800
Other (OTH)
AF:
AC:
0
AN:
59290
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74318 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152042
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
74318
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41474
American (AMR)
AF:
AC:
1
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5160
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67912
Other (OTH)
AF:
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PhyloP100
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at G2060 (P = 0.2645);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
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
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