20-62309371-C-T

Position:

chr20-62309371-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005560.6(LAMA5):c.11053G>A(p.Gly3685Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0108 in 1,590,316 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 8 hom., cov: 30)

Exomes 𝑓: 0.011 ( 101 hom. )

Consequence

LAMA5
NM_005560.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.66

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 links:

LAMA5 (HGNC:):

LAMA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02302304).

BP6

Variant 20-62309371-C-T is Benign according to our data. Variant chr20-62309371-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 279828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00855 (1300/152038) while in subpopulation NFE AF= 0.0127 (865/67978). AF 95% confidence interval is 0.012. There are 8 homozygotes in gnomad4. There are 596 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA5	NM_005560.6 linkuse as main transcript	c.11053G>A	p.Gly3685Arg	missense_variant	80/80	ENST00000252999.7	NP_005551.3	O15230-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAMA5	ENST00000252999.7 linkuse as main transcript	c.11053G>A	p.Gly3685Arg	missense_variant	80/80	1	NM_005560.6	ENSP00000252999.3	O15230-1
LAMA5	ENST00000370691.6 linkuse as main transcript	n.2848G>A		non_coding_transcript_exon_variant	17/17	1
LAMA5	ENST00000495695.1 linkuse as main transcript	n.554G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00856

AC:

1300

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00990

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00312

Gnomad FIN

AF:

0.0100

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.00845

AC:

1817

AN:

215090

Hom.:

AF XY:

0.00885

AC XY:

1053

AN XY:

118954

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.00717

Gnomad ASJ exome

AF:

0.00760

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00271

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.0110

AC:

15866

AN:

1438278

Hom.:

101

Cov.:

AF XY:

0.0108

AC XY:

7750

AN XY:

715040

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.00796

Gnomad4 ASJ exome

AF:

0.00844

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00261

Gnomad4 FIN exome

AF:

0.00987

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.00855

AC:

1300

AN:

152038

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

596

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.00988

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00313

Gnomad4 FIN

AF:

0.0100

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00769

Hom.:

Bravo

AF:

0.00889

ESP6500AA

AF:

0.00218

AC:

ESP6500EA

AF:

0.00883

AC:

ExAC

AF:

0.00815

AC:

965

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	LAMA5: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

LAMA5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 29, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.65

MetaRNN

Benign

0.023

MetaSVM

Uncertain

0.43

MutationAssessor

Pathogenic

3.2

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.6

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.86

MVP

0.83

ClinPred

0.035

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.78

gMVP

0.59

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over