6-129462497-C-T

Variant names:

• chr6-129462497-C-T
• rs7755729
• NM_000426.4:c.6993-1793C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000426.4(LAMA2):​c.6993-1793C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,760 control chromosomes in the GnomAD database, including 14,415 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 0.43 (14415 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.6993-1793C>T		intron_variant	Intron 49 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.6993-1793C>T		intron_variant	Intron 49 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.6993-1793C>T		intron_variant	Intron 49 of 64	5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65740 AN: 151642 Hom.: 14408 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.434 AC: 65796 AN: 151760 Hom.: 14415 Cov.: 31 AF XY: 0.432 AC XY: 32040 AN XY: 74160

African (AFR) AF: 0.430 AC: 17831 AN: 41434

American (AMR) AF: 0.414 AC: 6303 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1783 AN: 3466

East Asian (EAS) AF: 0.388 AC: 1984 AN: 5120

South Asian (SAS) AF: 0.464 AC: 2236 AN: 4814

European-Finnish (FIN) AF: 0.398 AC: 4195 AN: 10528

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30014 AN: 67874

Other (OTH) AF: 0.433 AC: 912 AN: 2106

Alfa AF: 0.446 Hom.: 20276

Bravo AF: 0.436

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.74
PhyloP100		-1.1
Mutation Taster		=99/1	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: rs7755729; hg19: chr6-129783642;