rs7776116

Variant names:

• chr6-128918625-T-C
• rs7776116
• NM_000426.4:c.112+35268T>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.112+35268T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,124 control chromosomes in the GnomAD database, including 5,741 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 0.22 (5741 hom., cov: 32)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.595
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 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.112+35268T>C		intron	N/A	NP_000417.3
	LAMA2	NM_001079823.2		c.112+35268T>C		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.112+35268T>C		intron	N/A	ENSP00000400365.2	P24043
	LAMA2	ENST00000618192.5	TSL:5	c.112+35268T>C		intron	N/A	ENSP00000480802.2	A0A087WX80
	LAMA2	ENST00000617695.5	TSL:5	c.112+35268T>C		intron	N/A	ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33857 AN: 152006 Hom.: 5711 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00539

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.223 AC: 33955 AN: 152124 Hom.: 5741 Cov.: 32 AF XY: 0.222 AC XY: 16501 AN XY: 74392

African (AFR) AF: 0.475 AC: 19705 AN: 41446

American (AMR) AF: 0.135 AC: 2058 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3470

East Asian (EAS) AF: 0.00540 AC: 28 AN: 5184

South Asian (SAS) AF: 0.172 AC: 829 AN: 4816

European-Finnish (FIN) AF: 0.148 AC: 1570 AN: 10600

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8476 AN: 68012

Other (OTH) AF: 0.223 AC: 470 AN: 2110

Alfa AF: 0.194 Hom.: 584

Bravo AF: 0.231

Asia WGS AF: 0.117 AC: 408 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.98
DANN	Benign	0.36
PhyloP100		-0.59
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: rs7776116; hg19: chr6-129239770;