rs6569603

Positions:

• chr6-129472572-C-A

Variant summary

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

The NM_000426.4(LAMA2):​c.7301-642C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,650 control chromosomes in the GnomAD database, including 14,741 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 0.44 (14741 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.7301-642C>A		intron_variant		ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.7301-642C>A		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.7301-642C>A		intron_variant		5	NM_000426.4	ENSP00000400365
	ENST00000665046.1	n.975+30033G>T		intron_variant, non_coding_transcript_variant
LAMA2	ENST00000617695.5	c.7301-642C>A		intron_variant		5		ENSP00000481744
LAMA2	ENST00000618192.5	c.7565-642C>A		intron_variant		5		ENSP00000480802	P1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66143 AN: 151530 Hom.: 14724 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.437 AC: 66213 AN: 151650 Hom.: 14741 Cov.: 31 AF XY: 0.436 AC XY: 32269 AN XY: 74088

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.449

Alfa AF: 0.426 Hom.: 6464

Bravo AF: 0.443

Asia WGS AF: 0.377 AC: 1312 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.0
DANN	Benign	0.78

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: rs6569603; hg19: chr6-129793717;