6-129228458-C-G

Variant names:

• chr6-129228458-C-G
• rs265334
• NM_000426.4:c.1783-21654C>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.1783-21654C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,920 control chromosomes in the GnomAD database, including 31,112 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 0.59 (31112 hom., cov: 31)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.1783-21654C>G		intron_variant	Intron 12 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.1783-21654C>G		intron_variant	Intron 12 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.1783-21654C>G		intron_variant	Intron 12 of 64	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.1783-21654C>G		intron_variant	Intron 12 of 65	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.1783-21654C>G		intron_variant	Intron 12 of 63	5		ENSP00000481744.2
LAMA2	ENST00000690881.1	n.1246-12083C>G		intron_variant	Intron 9 of 9

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89716 AN: 151802 Hom.: 31124 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.590 AC: 89707 AN: 151920 Hom.: 31112 Cov.: 31 AF XY: 0.595 AC XY: 44177 AN XY: 74256

African (AFR) AF: 0.202 AC: 8343 AN: 41398

American (AMR) AF: 0.703 AC: 10736 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2467 AN: 3464

East Asian (EAS) AF: 0.502 AC: 2583 AN: 5148

South Asian (SAS) AF: 0.705 AC: 3396 AN: 4814

European-Finnish (FIN) AF: 0.753 AC: 7947 AN: 10558

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52054 AN: 67962

Other (OTH) AF: 0.628 AC: 1325 AN: 2110

Alfa AF: 0.564 Hom.: 2051

Bravo AF: 0.564

Asia WGS AF: 0.582 AC: 2024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.30
PhyloP100		-0.39
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: rs265334; hg19: chr6-129549603;