20-62322431-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.6184G>A(p.Asp2062Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,587,292 control chromosomes in the GnomAD database, including 264,392 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 0.47 ( 19737 hom., cov: 34)

Exomes 𝑓: 0.58 ( 244655 hom. )

Consequence

LAMA5
NM_005560.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.15

Publications

33 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=1.5902873E-6).

BP6

Variant 20-62322431-C-T is Benign according to our data. Variant chr20-62322431-C-T is described in ClinVar as Benign. ClinVar VariationId is 1600279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA5	NM_005560.6 link	c.6184G>A	p.Asp2062Asn	missense_variant	Exon 47 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.6184G>A	p.Asp2062Asn	missense_variant	Exon 47 of 80	1	NM_005560.6	ENSP00000252999.3		O15230-1

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71072

AN:

151880

Hom.:

19737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.733

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.524

GnomAD2 exomes

AF:

0.565

AC:

114690

AN:

203158

AF XY:

0.573

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.546

Gnomad ASJ exome

AF:

0.615

Gnomad EAS exome

AF:

0.752

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.579

AC:

830496

AN:

1435294

Hom.:

244655

Cov.:

AF XY:

0.580

AC XY:

412759

AN XY:

711964

show subpopulations

African (AFR)

AF:

0.133

AC:

4411

AN:

33086

American (AMR)

AF:

0.539

AC:

22104

AN:

41016

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

15754

AN:

25512

East Asian (EAS)

AF:

0.744

AC:

28563

AN:

38388

South Asian (SAS)

AF:

0.577

AC:

47877

AN:

83032

European-Finnish (FIN)

AF:

0.593

AC:

29521

AN:

49774

Middle Eastern (MID)

AF:

0.562

AC:

3205

AN:

5698

European-Non Finnish (NFE)

AF:

0.587

AC:

645100

AN:

1099518

Other (OTH)

AF:

0.573

AC:

33961

AN:

59270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

19341

38682

58022

77363

96704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17702

35404

53106

70808

88510

<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:

0.468

AC:

71074

AN:

151998

Hom.:

19737

Cov.:

AF XY:

0.472

AC XY:

35039

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.151

AC:

6262

AN:

41468

American (AMR)

AF:

0.511

AC:

7812

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2161

AN:

3472

East Asian (EAS)

AF:

0.733

AC:

3781

AN:

5160

South Asian (SAS)

AF:

0.585

AC:

2822

AN:

4824

European-Finnish (FIN)

AF:

0.589

AC:

6242

AN:

10592

Middle Eastern (MID)

AF:

0.561

AC:

165

AN:

294

European-Non Finnish (NFE)

AF:

0.591

AC:

40120

AN:

67890

Other (OTH)

AF:

0.529

AC:

1117

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1695

3389

5084

6778

8473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.535

Hom.:

11020

Bravo

AF:

0.449

TwinsUK

AF:

0.589

AC:

2185

ALSPAC

AF:

0.583

AC:

2248

ESP6500AA

AF:

0.151

AC:

647

ESP6500EA

AF:

0.574

AC:

4883

ExAC

AF:

0.535

AC:

62613

Asia WGS

AF:

0.639

AC:

2224

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.037

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0000016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.89

PhyloP100

1.2

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

REVEL

Benign

0.044

Sift

Benign

0.082

Sift4G

Benign

0.26

Polyphen

0.13

Vest4

0.11

ClinPred

0.0091

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.15

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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