rs6940025

Positions:

• chr6-129166556-T-A

Variant summary

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

The NM_000426.4(LAMA2):​c.1306+881T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 152,232 control chromosomes in the GnomAD database, including 675 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 0.068 (675 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.1306+881T>A		intron_variant		ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.1306+881T>A		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.1306+881T>A		intron_variant		5	NM_000426.4	ENSP00000400365

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10395 AN: 152114 Hom.: 673 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0573

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

GnomAD4 genome AF: 0.0684 AC: 10420 AN: 152232 Hom.: 675 Cov.: 32 AF XY: 0.0668 AC XY: 4975 AN XY: 74456

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.0383

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0562

Alfa AF: 0.0511 Hom.: 51

Bravo AF: 0.0761

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.1
DANN	Benign	0.46

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: rs6940025; hg19: chr6-129487701;