6-128981426-T-C

Variant names:

• chr6-128981426-T-C
• rs9321142
• NM_000426.4:c.113-68492T>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.113-68492T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,722 control chromosomes in the GnomAD database, including 21,645 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 0.49 (21645 hom., cov: 29)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.989
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.113-68492T>C		intron_variant	Intron 1 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.113-68492T>C		intron_variant	Intron 1 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.113-68492T>C		intron_variant	Intron 1 of 64	5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74701 AN: 151602 Hom.: 21651 Cov.: 29

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.492 AC: 74693 AN: 151722 Hom.: 21645 Cov.: 29 AF XY: 0.500 AC XY: 37096 AN XY: 74122

African (AFR) AF: 0.168 AC: 6949 AN: 41372

American (AMR) AF: 0.622 AC: 9459 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1798 AN: 3464

East Asian (EAS) AF: 0.819 AC: 4216 AN: 5150

South Asian (SAS) AF: 0.617 AC: 2959 AN: 4792

European-Finnish (FIN) AF: 0.649 AC: 6834 AN: 10526

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.601 AC: 40774 AN: 67896

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.553 Hom.: 9851

Bravo AF: 0.474

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.69
DANN	Benign	0.77
PhyloP100		-0.99
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: rs9321142; hg19: chr6-129302571;