rs2571584

Variant names:

• chr6-129482340-A-G
• rs2571584
• NM_000426.4:c.7749+901A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-129482340-A-G
• chr6-129482340-A-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.7749+901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 151,924 control chromosomes in the GnomAD database, including 10,175 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 0.34 (10175 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• 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)

LOC124901401 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.7749+901A>G		intron_variant	Intron 55 of 64	ENST00000421865.3	NP_000417.3
LOC124901401	XR_007059767.1	n.4135T>C		non_coding_transcript_exon_variant	Exon 1 of 2
LAMA2	NM_001079823.2	c.7737+901A>G		intron_variant	Intron 54 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.7749+901A>G		intron_variant	Intron 55 of 64	5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52308 AN: 151806 Hom.: 10161 Cov.: 31

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.345 AC: 52360 AN: 151924 Hom.: 10175 Cov.: 31 AF XY: 0.345 AC XY: 25600 AN XY: 74242

African (AFR) AF: 0.538 AC: 22266 AN: 41410

American (AMR) AF: 0.299 AC: 4573 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3468

East Asian (EAS) AF: 0.302 AC: 1555 AN: 5156

South Asian (SAS) AF: 0.345 AC: 1660 AN: 4806

European-Finnish (FIN) AF: 0.302 AC: 3183 AN: 10550

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17498 AN: 67944

Other (OTH) AF: 0.313 AC: 660 AN: 2110

Alfa AF: 0.277 Hom.: 10923

Bravo AF: 0.353

Asia WGS AF: 0.321 AC: 1117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.85
PhyloP100		0.037
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: rs2571584; hg19: chr6-129803485;