chr6-129143875-G-A

Variant names:

• chr6-129143875-G-A
• rs7754560
• NM_000426.4:c.640-26G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000426.4(LAMA2):​c.640-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,502,734 control chromosomes in the GnomAD database, including 33,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5257 hom., cov: 32)
  • Exomes 𝑓: 0.20 (28701 hom.)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.303
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Myriad Women’s Health
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-129143875-G-A is Benign according to our data. Variant chr6-129143875-G-A is described in ClinVar as Benign. ClinVar VariationId is 256079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	NM_000426.4	MANE Select	c.640-26G>A		intron	N/A	NP_000417.3
	LAMA2	NM_001079823.2		c.640-26G>A		intron	N/A	NP_001073291.2	A0A087WYF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	ENST00000421865.3	TSL:5 MANE Select	c.640-26G>A		intron	N/A	ENSP00000400365.2	P24043
	LAMA2	ENST00000618192.5	TSL:5	c.640-26G>A		intron	N/A	ENSP00000480802.2	A0A087WX80
	LAMA2	ENST00000617695.5	TSL:5	c.640-26G>A		intron	N/A	ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37442 AN: 151730 Hom.: 5257 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.229

GnomAD2 exomes AF: 0.193 AC: 45623 AN: 236086 AF XY: 0.196

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.130

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.202 AC: 272252 AN: 1350886 Hom.: 28701 Cov.: 20 AF XY: 0.203 AC XY: 137054 AN XY: 676704

African (AFR) AF: 0.384 AC: 11582 AN: 30140

American (AMR) AF: 0.123 AC: 5212 AN: 42508

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4567 AN: 25054

East Asian (EAS) AF: 0.143 AC: 5537 AN: 38826

South Asian (SAS) AF: 0.240 AC: 19289 AN: 80354

European-Finnish (FIN) AF: 0.202 AC: 10639 AN: 52634

Middle Eastern (MID) AF: 0.240 AC: 1321 AN: 5498

European-Non Finnish (NFE) AF: 0.198 AC: 202330 AN: 1019428

Other (OTH) AF: 0.209 AC: 11775 AN: 56444

GnomAD4 genome AF: 0.247 AC: 37480 AN: 151848 Hom.: 5257 Cov.: 32 AF XY: 0.244 AC XY: 18108 AN XY: 74222

African (AFR) AF: 0.391 AC: 16181 AN: 41392

American (AMR) AF: 0.170 AC: 2587 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 660 AN: 3454

East Asian (EAS) AF: 0.140 AC: 723 AN: 5158

South Asian (SAS) AF: 0.247 AC: 1187 AN: 4812

European-Finnish (FIN) AF: 0.204 AC: 2156 AN: 10556

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13347 AN: 67916

Other (OTH) AF: 0.232 AC: 489 AN: 2108

Alfa AF: 0.205 Hom.: 651

Bravo AF: 0.249

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.61
PhyloP100		0.30
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: rs7754560; hg19: chr6-129465020; COSMIC: COSV70355579;