chr20-62319414-C-T

Variant names:

• chr20-62319414-C-T
• rs2297588
• NM_005560.6:c.6871+270G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005560.6(LAMA5):​c.6871+270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,942 control chromosomes in the GnomAD database, including 5,270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5270 hom., cov: 32)
• Consequence: LAMA5 NM_005560.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA5	NM_005560.6	c.6871+270G>A		intron_variant	Intron 51 of 79	ENST00000252999.7	NP_005551.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA5	ENST00000252999.7	c.6871+270G>A		intron_variant	Intron 51 of 79	1	NM_005560.6	ENSP00000252999.3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39396 AN: 151826 Hom.: 5270 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39412 AN: 151942 Hom.: 5270 Cov.: 32 AF XY: 0.253 AC XY: 18802 AN XY: 74266

African (AFR) AF: 0.218 AC: 9018 AN: 41436

American (AMR) AF: 0.237 AC: 3609 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1035 AN: 5148

South Asian (SAS) AF: 0.229 AC: 1101 AN: 4812

European-Finnish (FIN) AF: 0.230 AC: 2427 AN: 10568

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20535 AN: 67946

Other (OTH) AF: 0.267 AC: 563 AN: 2112

Alfa AF: 0.285 Hom.: 4534

Bravo AF: 0.259

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.014
DANN	Benign	0.61
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs2297588; hg19: chr20-60894470;