rs11967042

Variant names:

• chr6-129297914-G-A
• rs11967042
• NM_000426.4:c.3037+49G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-129297914-G-A
• chr6-129297914-G-T

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.3037+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,504,734 control chromosomes in the GnomAD database, including 11,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1433 hom., cov: 33)
  • Exomes 𝑓: 0.10 (9632 hom.)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.36
• Publications: 7 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=-0.92).
• BP6: Variant 6-129297914-G-A is Benign according to our data. Variant chr6-129297914-G-A is described in ClinVar as Benign. ClinVar VariationId is 256063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) 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.3037+49G>A		intron	N/A	NP_000417.3
	LAMA2	NM_001079823.2		c.3037+49G>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.3037+49G>A		intron	N/A	ENSP00000400365.2	P24043
	LAMA2	ENST00000618192.5	TSL:5	c.3301+49G>A		intron	N/A	ENSP00000480802.2	A0A087WX80
	LAMA2	ENST00000617695.5	TSL:5	c.3037+49G>A		intron	N/A	ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17728 AN: 151976 Hom.: 1430 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0972

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.143 AC: 30729 AN: 214394 AF XY: 0.135

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.277

Gnomad ASJ exome AF: 0.0966

Gnomad EAS exome AF: 0.390

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.0800

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.102 AC: 137753 AN: 1352640 Hom.: 9632 Cov.: 20 AF XY: 0.101 AC XY: 68130 AN XY: 676048

African (AFR) AF: 0.114 AC: 3591 AN: 31562

American (AMR) AF: 0.267 AC: 11011 AN: 41180

Ashkenazi Jewish (ASJ) AF: 0.0990 AC: 2497 AN: 25210

East Asian (EAS) AF: 0.386 AC: 15024 AN: 38926

South Asian (SAS) AF: 0.101 AC: 8263 AN: 81442

European-Finnish (FIN) AF: 0.133 AC: 6837 AN: 51398

Middle Eastern (MID) AF: 0.121 AC: 678 AN: 5582

European-Non Finnish (NFE) AF: 0.0816 AC: 83315 AN: 1020582

Other (OTH) AF: 0.115 AC: 6537 AN: 56758

GnomAD4 genome AF: 0.117 AC: 17749 AN: 152094 Hom.: 1433 Cov.: 33 AF XY: 0.123 AC XY: 9121 AN XY: 74350

African (AFR) AF: 0.111 AC: 4626 AN: 41496

American (AMR) AF: 0.202 AC: 3079 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0972 AC: 337 AN: 3468

East Asian (EAS) AF: 0.401 AC: 2070 AN: 5168

South Asian (SAS) AF: 0.111 AC: 534 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1372 AN: 10564

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5375 AN: 67990

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.0994 Hom.: 1764

Bravo AF: 0.126

Asia WGS AF: 0.202 AC: 706 AN: 3478

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	-0.92
CADD	Benign	0.093
DANN	Benign	0.44
PhyloP100		-2.4
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: rs11967042; hg19: chr6-129619059;