rs12193446

Positions:

• chr6-129498893-A-G

Variant summary

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

The NM_000426.4(LAMA2):​c.8245-3766A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 152,210 control chromosomes in the GnomAD database, including 424 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 0.063 (424 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4	c.8245-3766A>G		intron_variant		ENST00000421865.3
LOC102723409	XR_001743860.2	n.12289+3712T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3	c.8245-3766A>G		intron_variant		5	NM_000426.4
	ENST00000665046.1	n.975+3712T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0633 AC: 9631 AN: 152092 Hom.: 424 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0633 AC: 9631 AN: 152210 Hom.: 424 Cov.: 32 AF XY: 0.0636 AC XY: 4736 AN XY: 74412

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.0480

Gnomad4 ASJ AF: 0.0978

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0251

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0805 Hom.: 261

Bravo AF: 0.0562

Asia WGS AF: 0.0160 AC: 54 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.54

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: rs12193446; hg19: chr6-129820038; COSMIC: COSV70343181;