rs17799083

chr6-129351991-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000426.4(LAMA2):c.4524-1173A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,218 control chromosomes in the GnomAD database, including 2,245 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 0.15 (2245 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871

Genes affected

LAMA2 (HGNC:6482): (laminin subunit alpha 2) Laminin, an extracellular protein, is a major component of the basement membrane. It is thought to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. It is composed of three subunits, alpha, beta, and gamma, which are bound to each other by disulfide bonds into a cross-shaped molecule. This gene encodes the alpha 2 chain, which constitutes one of the subunits of laminin 2 (merosin) and laminin 4 (s-merosin). Mutations in this gene have been identified as the cause of congenital merosin-deficient muscular dystrophy. Two transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4	c.4524-1173A>C		intron_variant		ENST00000421865.3
LAMA2	NM_001079823.2	c.4524-1173A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3	c.4524-1173A>C		intron_variant		5	NM_000426.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23179 AN: 152096 Hom.: 2245 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.152 AC: 23177 AN: 152218 Hom.: 2245 Cov.: 32 AF XY: 0.151 AC XY: 11245 AN XY: 74418

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.0389

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.142

Alfa AF: 0.202 Hom.: 6557

Bravo AF: 0.139

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	15
Dann	Benign	0.82

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

Other links and lift over

dbSNP: rs17799083; hg19: chr6-129673136;