chr20-62335024-G-C

Variant names:

• chr20-62335024-G-C
• rs193920947
• NM_005560.6:c.2479C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005560.6(LAMA5):​c.2479C>G​(p.Arg827Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,460,266 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R827H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LAMA5 NM_005560.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63
• 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 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005560.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA5	NM_005560.6	MANE Select	c.2479C>G	p.Arg827Gly	missense	Exon 20 of 80	NP_005551.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA5	ENST00000252999.7	TSL:1 MANE Select	c.2479C>G	p.Arg827Gly	missense	Exon 20 of 80	ENSP00000252999.3
	LAMA5	ENST00000474128.1	TSL:3	n.*318C>G		non_coding_transcript_exon	Exon 6 of 8	ENSP00000420069.1
	LAMA5	ENST00000474128.1	TSL:3	n.*318C>G		3_prime_UTR	Exon 6 of 8	ENSP00000420069.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460266 Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11 AN XY: 726464

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1111484

Other (OTH) AF: 0.00 AC: 0 AN: 60328

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.026
Eigen_PC	Benign	0.072
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		5.6
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.16
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.32	B
Vest4		0.48
MutPred		0.54		Loss of loop (P = 0.1242)
MVP		0.56
ClinPred		0.97	D
GERP RS		4.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.34
gMVP		0.51
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs193920947; hg19: chr20-60910080;