chr20-62310186-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_005560.6(LAMA5):c.10726G>A(p.Glu3576Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,612,484 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 17 hom. )

Consequence

LAMA5
NM_005560.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.618

Publications

14 publications found

Variant links:

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 26
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
LAMA5-related multisystemic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LAMA5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006543368).

BP6

Variant 20-62310186-C-T is Benign according to our data. Variant chr20-62310186-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 438605.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00384 (585/152314) while in subpopulation NFE AF = 0.00616 (419/68010). AF 95% confidence interval is 0.00567. There are 4 homozygotes in GnomAd4. There are 260 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA5	NM_005560.6 link	c.10726G>A	p.Glu3576Lys	missense_variant	Exon 77 of 80	ENST00000252999.7	NP_005551.3	O15230-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA5	ENST00000252999.7 link	c.10726G>A	p.Glu3576Lys	missense_variant	Exon 77 of 80	1	NM_005560.6	ENSP00000252999.3	O15230-1
LAMA5	ENST00000370691.6 link	n.2521G>A		non_coding_transcript_exon_variant	Exon 14 of 17	1
LAMA5	ENST00000495695.1 link	n.227G>A		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

585

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00616

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00324

AC:

803

AN:

248092

AF XY:

0.00329

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00584

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00323

Gnomad NFE exome

AF:

0.00482

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00485

AC:

7083

AN:

1460170

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

3438

AN XY:

726362

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33480

American (AMR)

AF:

0.00188

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00677

AC:

177

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000916

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00365

AC:

189

AN:

51798

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00564

AC:

6267

AN:

1111956

Other (OTH)

AF:

0.00424

AC:

256

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

449

898

1348

1797

2246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00384

AC:

585

AN:

152314

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

260

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41578

American (AMR)

AF:

0.00183

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00616

AC:

419

AN:

68010

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00476

Hom.:

Bravo

AF:

0.00329

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00582

AC:

ExAC

AF:

0.00285

AC:

345

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00523

EpiControl

AF:

0.00486

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LAMA5: BP4, BS2 -

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polymicrogyria

Uncertain:1

Sep 01, 2017

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

this variant was indentified in an individual with malformations of cortical development -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.12

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.48

M_CAP

Benign

0.063

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.64

PhyloP100

0.62

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

REVEL

Benign

0.22

Sift

Benign

0.48

Sift4G

Benign

0.77

Polyphen

0.28

Vest4

0.13

MVP

0.38

ClinPred

0.0017

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.048

gMVP

0.50

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over