chr6-129472572-C-A

Variant names:

• chr6-129472572-C-A
• rs6569603
• NM_000426.4:c.7301-642C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• congenital merosin-deficient muscular dystrophy 1A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, G2P
• LAMA2-related muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• muscular dystrophy, limb-girdle, autosomal recessive 23

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000226149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.7301-642C>A		intron_variant	Intron 51 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.7301-642C>A		intron_variant	Intron 51 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.7301-642C>A		intron_variant	Intron 51 of 64	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.7565-642C>A		intron_variant	Intron 52 of 65	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.7301-642C>A		intron_variant	Intron 51 of 63	5		ENSP00000481744.2
ENSG00000226149	ENST00000665046.1	n.975+30033G>T		intron_variant	Intron 9 of 9

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

African (AFR) AF: 0.515 AC: 21322 AN: 41396

American (AMR) AF: 0.411 AC: 6251 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1929 AN: 3466

East Asian (EAS) AF: 0.305 AC: 1570 AN: 5144

South Asian (SAS) AF: 0.454 AC: 2184 AN: 4806

European-Finnish (FIN) AF: 0.367 AC: 3874 AN: 10564

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27763 AN: 67740

Other (OTH) AF: 0.449 AC: 947 AN: 2108

Alfa AF: 0.427 Hom.: 7284

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
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6569603; hg19: chr6-129793717;