rs9492296

Variant names:

• chr6-129288092-T-C
• rs9492296
• NM_000426.4:c.2749+34T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-129288092-T-C
• chr6-129288092-T-G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000426.4(LAMA2):​c.2749+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,568,068 control chromosomes in the GnomAD database, including 437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (213 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (224 hom.)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.449
• Publications: 1 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 6-129288092-T-C is Benign according to our data. Variant chr6-129288092-T-C is described in ClinVar as Benign. ClinVar VariationId is 256060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.2749+34T>C		intron	N/A	NP_000417.3
	LAMA2	NM_001079823.2		c.2749+34T>C		intron	N/A	NP_001073291.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA2	ENST00000421865.3	TSL:5 MANE Select	c.2749+34T>C		intron	N/A	ENSP00000400365.2
	LAMA2	ENST00000618192.5	TSL:5	c.2749+34T>C		intron	N/A	ENSP00000480802.2
	LAMA2	ENST00000617695.5	TSL:5	c.2749+34T>C		intron	N/A	ENSP00000481744.2

Frequencies

GnomAD3 genomes AF: 0.0315 AC: 4796 AN: 152172 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.00914 AC: 2284 AN: 249810 AF XY: 0.00697

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.00637

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000695

Gnomad OTH exome AF: 0.00753

GnomAD4 exome AF: 0.00407 AC: 5761 AN: 1415778 Hom.: 224 Cov.: 25 AF XY: 0.00385 AC XY: 2722 AN XY: 707272

African (AFR) AF: 0.108 AC: 3521 AN: 32492

American (AMR) AF: 0.00706 AC: 315 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00143 AC: 37 AN: 25842

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39478

South Asian (SAS) AF: 0.00595 AC: 507 AN: 85204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.0100 AC: 57 AN: 5682

European-Non Finnish (NFE) AF: 0.000727 AC: 778 AN: 1070220

Other (OTH) AF: 0.00926 AC: 545 AN: 58850

GnomAD4 genome AF: 0.0316 AC: 4819 AN: 152290 Hom.: 213 Cov.: 32 AF XY: 0.0306 AC XY: 2282 AN XY: 74486

African (AFR) AF: 0.106 AC: 4412 AN: 41536

American (AMR) AF: 0.0136 AC: 208 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000941 AC: 64 AN: 68026

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.0217 Hom.: 56

Bravo AF: 0.0357

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.36
CADD	Benign	16
DANN	Benign	0.59
PhyloP100		0.45
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: rs9492296; hg19: chr6-129609237;