6-129228458-C-G

Variant summary

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

The NM_000426.4(LAMA2):c.1783-21654C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,920 control chromosomes in the GnomAD database, including 31,112 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 0.59 (31112 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA2	NM_000426.4	c.1783-21654C>G		intron_variant		ENST00000421865.3
LAMA2	NM_001079823.2	c.1783-21654C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA2	ENST00000421865.3	c.1783-21654C>G		intron_variant		5	NM_000426.4
LAMA2	ENST00000617695.5	c.1783-21654C>G		intron_variant		5
LAMA2	ENST00000618192.5	c.1783-21654C>G		intron_variant		5		P1
LAMA2	ENST00000690881.1	n.1246-12083C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89716 AN: 151802 Hom.: 31124 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.590 AC: 89707 AN: 151920 Hom.: 31112 Cov.: 31 AF XY: 0.595 AC XY: 44177 AN XY: 74256

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.628

Alfa AF: 0.564 Hom.: 2051

Bravo AF: 0.564

Asia WGS AF: 0.582 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.30

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: rs265334; hg19: chr6-129549603;