rs2571577

Variant names:

• chr6-129476939-T-C
• rs2571577
• NM_000426.4:c.7451+1538T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-129476939-T-C
• chr6-129476939-T-G

Variant summary

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

The NM_000426.4(LAMA2):​c.7451+1538T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,008 control chromosomes in the GnomAD database, including 3,398 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 0.21 (3398 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• 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)

ENSG00000226149 (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 (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.7451+1538T>C		intron_variant	Intron 53 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.7440-1754T>C		intron_variant	Intron 52 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.7451+1538T>C		intron_variant	Intron 53 of 64	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.7715+1538T>C		intron_variant	Intron 54 of 65	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.7440-1754T>C		intron_variant	Intron 52 of 63	5		ENSP00000481744.2
ENSG00000226149	ENST00000665046.1	n.975+25666A>G		intron_variant	Intron 9 of 9

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31407 AN: 151890 Hom.: 3400 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.207 AC: 31409 AN: 152008 Hom.: 3398 Cov.: 32 AF XY: 0.210 AC XY: 15576 AN XY: 74288

African (AFR) AF: 0.187 AC: 7750 AN: 41492

American (AMR) AF: 0.266 AC: 4051 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1547 AN: 5140

South Asian (SAS) AF: 0.333 AC: 1602 AN: 4812

European-Finnish (FIN) AF: 0.194 AC: 2045 AN: 10566

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13274 AN: 67964

Other (OTH) AF: 0.209 AC: 440 AN: 2110

Alfa AF: 0.197 Hom.: 5275

Bravo AF: 0.208

Asia WGS AF: 0.293 AC: 1019 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	3.5
DANN	Benign	0.65
PhyloP100		-0.054
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: rs2571577; hg19: chr6-129798084;