rs12205363

chr6-129513484-T-Cchr6-129513484-T-G

Variant summary

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

The NM_000426.4(LAMA2):c.8989-889T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 152,276 control chromosomes in the GnomAD database, including 244 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 0.050 (244 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4	c.8989-889T>C		intron_variant		ENST00000421865.3
LOC102723409	XR_001743860.2	n.12102+8993A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3	c.8989-889T>C		intron_variant		5	NM_000426.4
	ENST00000665046.1	n.788+8993A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7670 AN: 152158 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0641

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0505 AC: 7685 AN: 152276 Hom.: 244 Cov.: 32 AF XY: 0.0511 AC XY: 3806 AN XY: 74462

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.0505

Gnomad4 ASJ AF: 0.0641

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.0209

Gnomad4 FIN AF: 0.0888

Gnomad4 NFE AF: 0.0675

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0592 Hom.: 391

Bravo AF: 0.0460

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.2
Dann	Benign	0.67

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: rs12205363; hg19: chr6-129834629; COSMIC: COSV70343187;