rs17799083

Variant names:

• chr6-129351991-A-C
• rs17799083
• NM_000426.4:c.4524-1173A>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.4524-1173A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,218 control chromosomes in the GnomAD database, including 2,245 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 0.15 (2245 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.4524-1173A>C		intron_variant	Intron 31 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.4524-1173A>C		intron_variant	Intron 31 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.4524-1173A>C		intron_variant	Intron 31 of 64	5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23179 AN: 152096 Hom.: 2245 Cov.: 32

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.152 AC: 23177 AN: 152218 Hom.: 2245 Cov.: 32 AF XY: 0.151 AC XY: 11245 AN XY: 74418

African (AFR) AF: 0.0515 AC: 2138 AN: 41552

American (AMR) AF: 0.133 AC: 2032 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 507 AN: 3472

East Asian (EAS) AF: 0.0389 AC: 202 AN: 5190

South Asian (SAS) AF: 0.170 AC: 820 AN: 4828

European-Finnish (FIN) AF: 0.210 AC: 2223 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14780 AN: 67990

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.191 Hom.: 9615

Bravo AF: 0.139

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		0.87
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: rs17799083; hg19: chr6-129673136;