rs3798663

Variant names:

• chr6-129313110-G-A
• rs3798663
• NM_000426.4:c.3411+13G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-129313110-G-A
• chr6-129313110-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000426.4(LAMA2):​c.3411+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,520,938 control chromosomes in the GnomAD database, including 30,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6769 hom., cov: 33)
  • Exomes 𝑓: 0.16 (23802 hom.)
• Consequence: LAMA2 NM_000426.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-129313110-G-A is Benign according to our data. Variant chr6-129313110-G-A is described in ClinVar as [Benign]. Clinvar id is 92951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129313110-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.3411+13G>A		intron_variant	Intron 23 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.3411+13G>A		intron_variant	Intron 23 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.3411+13G>A		intron_variant	Intron 23 of 64	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.3675+13G>A		intron_variant	Intron 24 of 65	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.3411+13G>A		intron_variant	Intron 23 of 63	5		ENSP00000481744.2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38619 AN: 151972 Hom.: 6752 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.222 AC: 52098 AN: 234696 Hom.: 8160 AF XY: 0.209 AC XY: 26382 AN XY: 126370

Gnomad AFR exome AF: 0.463

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.552

Gnomad SAS exome AF: 0.186

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.162 AC: 221945 AN: 1368848 Hom.: 23802 Cov.: 21 AF XY: 0.161 AC XY: 109445 AN XY: 679364

Gnomad4 AFR exome AF: 0.469

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.254 AC: 38680 AN: 152090 Hom.: 6769 Cov.: 33 AF XY: 0.258 AC XY: 19201 AN XY: 74372

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.242

Alfa AF: 0.206 Hom.: 1119

Bravo AF: 0.280

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 25, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jan 20, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Merosin deficient congenital muscular dystrophy Benign:2

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

LAMA2-related muscular dystrophy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital muscular dystrophy due to partial LAMA2 deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Muscular dystrophy, limb-girdle, autosomal recessive 23 Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.22
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs3798663; hg19: chr6-129634255; COSMIC: COSV70347843;