6-128981426-T-C

Position:

• chr6-128981426-T-C

Variant summary

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

The NM_000426.4(LAMA2):​c.113-68492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,722 control chromosomes in the GnomAD database, including 21,645 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 0.49 (21645 hom., cov: 29)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989

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]

LAMA2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.113-68492T>C		intron_variant		ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.113-68492T>C		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.113-68492T>C		intron_variant		5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74701 AN: 151602 Hom.: 21651 Cov.: 29

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.492 AC: 74693 AN: 151722 Hom.: 21645 Cov.: 29 AF XY: 0.500 AC XY: 37096 AN XY: 74122

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.485

Alfa AF: 0.550 Hom.: 6308

Bravo AF: 0.474

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.69
DANN	Benign	0.77

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: rs9321142; hg19: chr6-129302571;