NM_000426.4:c.113-40651T>C

Variant names:

• chr6-129009267-T-C
• rs6912590
• NM_000426.4:c.113-40651T>C

Variant summary

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

The NM_000426.4(LAMA2):​c.113-40651T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 152,146 control chromosomes in the GnomAD database, including 64,705 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 0.92 (64705 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	NM_000426.4	MANE Select	c.113-40651T>C		intron	N/A	NP_000417.3
	LAMA2	NM_001079823.2		c.113-40651T>C		intron	N/A	NP_001073291.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	ENST00000421865.3	TSL:5 MANE Select	c.113-40651T>C		intron	N/A	ENSP00000400365.2
	LAMA2	ENST00000618192.5	TSL:5	c.113-40651T>C		intron	N/A	ENSP00000480802.2
	LAMA2	ENST00000617695.5	TSL:5	c.113-40651T>C		intron	N/A	ENSP00000481744.2

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139757 AN: 152028 Hom.: 64671 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.939

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.987

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.920

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

GnomAD4 genome AF: 0.919 AC: 139853 AN: 152146 Hom.: 64705 Cov.: 31 AF XY: 0.920 AC XY: 68427 AN XY: 74376

African (AFR) AF: 0.801 AC: 33221 AN: 41486

American (AMR) AF: 0.951 AC: 14536 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.939 AC: 3260 AN: 3472

East Asian (EAS) AF: 0.972 AC: 5030 AN: 5176

South Asian (SAS) AF: 0.907 AC: 4362 AN: 4808

European-Finnish (FIN) AF: 0.987 AC: 10462 AN: 10596

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65862 AN: 68014

Other (OTH) AF: 0.921 AC: 1944 AN: 2110

Alfa AF: 0.938 Hom.: 8319

Bravo AF: 0.912

Asia WGS AF: 0.928 AC: 3219 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.42
PhyloP100		0.26
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: rs6912590; hg19: chr6-129330412; COSMIC: COSV70356568;