rs2571584

Positions:

• chr6-129482340-A-G
• chr6-129482340-A-T

Variant summary

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

The NM_000426.4(LAMA2):​c.7749+901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,924 control chromosomes in the GnomAD database, including 10,175 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 0.34 (10175 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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]

LOC124901401 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.7749+901A>G		intron_variant		ENST00000421865.3	NP_000417.3
LOC124901401	XR_007059767.1	n.4135T>C		non_coding_transcript_exon_variant	1/2
LAMA2	NM_001079823.2	c.7737+901A>G		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.7749+901A>G		intron_variant		5	NM_000426.4	ENSP00000400365
	ENST00000665046.1	n.975+20265T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52308 AN: 151806 Hom.: 10161 Cov.: 31

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.345 AC: 52360 AN: 151924 Hom.: 10175 Cov.: 31 AF XY: 0.345 AC XY: 25600 AN XY: 74242

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.313

Alfa AF: 0.277 Hom.: 2932

Bravo AF: 0.353

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.85

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: rs2571584; hg19: chr6-129803485;