6-129462497-C-T

Variant summary

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

The NM_000426.4(LAMA2):c.6993-1793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,760 control chromosomes in the GnomAD database, including 14,415 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 0.43 (14415 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4	c.6993-1793C>T		intron_variant		ENST00000421865.3
LAMA2	NM_001079823.2	c.6993-1793C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3	c.6993-1793C>T		intron_variant		5	NM_000426.4
	ENST00000665046.1	n.976-21245G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65740 AN: 151642 Hom.: 14408 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.434 AC: 65796 AN: 151760 Hom.: 14415 Cov.: 31 AF XY: 0.432 AC XY: 32040 AN XY: 74160

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.433

Alfa AF: 0.445 Hom.: 14630

Bravo AF: 0.436

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.51
Dann	Benign	0.74

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: rs7755729; hg19: chr6-129783642;