6-129166556-T-A

Variant names:

• chr6-129166556-T-A
• rs6940025
• NM_000426.4:c.1306+881T>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.1306+881T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 152,232 control chromosomes in the GnomAD database, including 675 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 0.068 (675 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 2 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	NM_000426.4	MANE Select	c.1306+881T>A		intron	N/A	NP_000417.3
	LAMA2	NM_001079823.2		c.1306+881T>A		intron	N/A	NP_001073291.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	ENST00000421865.3	TSL:5 MANE Select	c.1306+881T>A		intron	N/A	ENSP00000400365.2
	LAMA2	ENST00000686577.1		n.2253T>A		non_coding_transcript_exon	Exon 9 of 9
	LAMA2	ENST00000618192.5	TSL:5	c.1306+881T>A		intron	N/A	ENSP00000480802.2

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10395 AN: 152114 Hom.: 673 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0383

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0573

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

GnomAD4 genome AF: 0.0684 AC: 10420 AN: 152232 Hom.: 675 Cov.: 32 AF XY: 0.0668 AC XY: 4975 AN XY: 74456

African (AFR) AF: 0.170 AC: 7072 AN: 41510

American (AMR) AF: 0.0383 AC: 585 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.0249 AC: 129 AN: 5186

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4828

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1976 AN: 68018

Other (OTH) AF: 0.0562 AC: 119 AN: 2116

Alfa AF: 0.0511 Hom.: 51

Bravo AF: 0.0761

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.1
DANN	Benign	0.46
PhyloP100		0.49
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: rs6940025; hg19: chr6-129487701;