20-62324150-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005560.6(LAMA5):c.5698G>A(p.Val1900Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,556,012 control chromosomes in the GnomAD database, including 364,673 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32341 hom., cov: 28)

Exomes 𝑓: 0.69 ( 332332 hom. )

Consequence

LAMA5
NM_005560.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.328

Publications

45 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.248138E-6).

BP6

Variant 20-62324150-C-T is Benign according to our data. Variant chr20-62324150-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA5	NM_005560.6 link	c.5698G>A	p.Val1900Met	missense_variant	Exon 43 of 80	ENST00000252999.7	NP_005551.3	O15230-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA5	ENST00000252999.7 link	c.5698G>A	p.Val1900Met	missense_variant	Exon 43 of 80	1	NM_005560.6	ENSP00000252999.3		O15230-1
LAMA5	ENST00000464134.1 link	n.486G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.653

AC:

97611

AN:

149454

Hom.:

32333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.539

Gnomad AMI

AF:

0.767

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.752

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.648

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.684

GnomAD2 exomes

AF:

0.683

AC:

138439

AN:

202720

AF XY:

0.684

show subpopulations

Gnomad AFR exome

AF:

0.531

Gnomad AMR exome

AF:

0.741

Gnomad ASJ exome

AF:

0.747

Gnomad EAS exome

AF:

0.781

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.689

Gnomad OTH exome

AF:

0.698

GnomAD4 exome

AF:

0.686

AC:

965300

AN:

1406438

Hom.:

332332

Cov.:

AF XY:

0.685

AC XY:

478209

AN XY:

698236

show subpopulations

African (AFR)

AF:

0.541

AC:

16357

AN:

30248

American (AMR)

AF:

0.734

AC:

21216

AN:

28900

Ashkenazi Jewish (ASJ)

AF:

0.746

AC:

17431

AN:

23354

East Asian (EAS)

AF:

0.775

AC:

29822

AN:

38460

South Asian (SAS)

AF:

0.636

AC:

49582

AN:

77968

European-Finnish (FIN)

AF:

0.659

AC:

33856

AN:

51380

Middle Eastern (MID)

AF:

0.716

AC:

3965

AN:

5536

European-Non Finnish (NFE)

AF:

0.689

AC:

752911

AN:

1092718

Other (OTH)

AF:

0.694

AC:

40160

AN:

57874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

16316

32631

48947

65262

81578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19446

38892

58338

77784

97230

<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:

0.653

AC:

97648

AN:

149574

Hom.:

32341

Cov.:

AF XY:

0.652

AC XY:

47501

AN XY:

72826

show subpopulations

African (AFR)

AF:

0.538

AC:

21914

AN:

40698

American (AMR)

AF:

0.717

AC:

10687

AN:

14912

Ashkenazi Jewish (ASJ)

AF:

0.752

AC:

2608

AN:

3468

East Asian (EAS)

AF:

0.775

AC:

3933

AN:

5078

South Asian (SAS)

AF:

0.638

AC:

2735

AN:

4286

European-Finnish (FIN)

AF:

0.648

AC:

6727

AN:

10382

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

46740

AN:

67510

Other (OTH)

AF:

0.687

AC:

1405

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1662

3324

4986

6648

8310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.685

Hom.:

73911

Bravo

AF:

0.655

TwinsUK

AF:

0.695

AC:

2576

ALSPAC

AF:

0.686

AC:

2643

ESP6500AA

AF:

0.543

AC:

2384

ESP6500EA

AF:

0.701

AC:

5993

ExAC

AF:

0.679

AC:

81754

Asia WGS

AF:

0.704

AC:

2448

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0000022

MetaSVM

Benign

-0.99

MutationAssessor

Benign

2.0

PhyloP100

0.33

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.99

REVEL

Benign

0.064

Sift

Benign

0.18

Sift4G

Uncertain

0.059

Polyphen

0.84

Vest4

0.061

ClinPred

0.0057

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.035

gMVP

0.11

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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