6-128918625-T-C

Position:

• chr6-128918625-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.112+35268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,124 control chromosomes in the GnomAD database, including 5,741 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 0.22 (5741 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.112+35268T>C		intron_variant		ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.112+35268T>C		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.112+35268T>C		intron_variant		5	NM_000426.4	ENSP00000400365

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33857 AN: 152006 Hom.: 5711 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.223 AC: 33955 AN: 152124 Hom.: 5741 Cov.: 32 AF XY: 0.222 AC XY: 16501 AN XY: 74392

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.00540

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.223

Alfa AF: 0.184 Hom.: 501

Bravo AF: 0.231

Asia WGS AF: 0.117 AC: 408 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.98
DANN	Benign	0.36

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: rs7776116; hg19: chr6-129239770;