6-129009267-T-C

Position:

• chr6-129009267-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.113-40651T>C		intron_variant		ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.113-40651T>C		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.113-40651T>C		intron_variant		5	NM_000426.4	ENSP00000400365

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

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.939

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.907

Gnomad4 FIN AF: 0.987

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.921

Alfa AF: 0.943 Hom.: 8068

Bravo AF: 0.912

Asia WGS AF: 0.928 AC: 3219 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs6912590; hg19: chr6-129330412; COSMIC: COSV70356568;