rs34997144

Variant names:

• chr6-129492363-T-A
• rs34997144
• NM_000426.4:c.8124T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-129492363-T-A
• chr6-129492363-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000426.4(LAMA2):​c.8124T>A​(p.Gly2708Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,614,160 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (44 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (57 hom.)
• Consequence: LAMA2 NM_000426.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.184

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]

ENSG00000226149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 6-129492363-T-A is Benign according to our data. Variant chr6-129492363-T-A is described in ClinVar as [Benign]. Clinvar id is 129444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129492363-T-A is described in Lovd as [Benign]. Variant chr6-129492363-T-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.184 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.8124T>A	p.Gly2708Gly	synonymous_variant	Exon 58 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.8112T>A	p.Gly2704Gly	synonymous_variant	Exon 57 of 64		NP_001073291.2
LOC102723409	XR_001743860.2	n.*119A>T		downstream_gene_variant
LOC102723409	XR_007059756.1	n.*119A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.8124T>A	p.Gly2708Gly	synonymous_variant	Exon 58 of 65	5	NM_000426.4	ENSP00000400365.2

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2411 AN: 152222 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00436 AC: 1095 AN: 251012 Hom.: 27 AF XY: 0.00310 AC XY: 421 AN XY: 135652

Gnomad AFR exome AF: 0.0502

Gnomad AMR exome AF: 0.00538

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000591

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00186 AC: 2714 AN: 1461820 Hom.: 57 Cov.: 32 AF XY: 0.00161 AC XY: 1173 AN XY: 727218

Gnomad4 AFR exome AF: 0.0515

Gnomad4 AMR exome AF: 0.00550

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000366

Gnomad4 OTH exome AF: 0.00411

GnomAD4 genome AF: 0.0159 AC: 2418 AN: 152340 Hom.: 44 Cov.: 32 AF XY: 0.0157 AC XY: 1167 AN XY: 74500

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00130 Hom.: 0

Bravo AF: 0.0178

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Jun 01, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Jul 08, 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. -

-

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

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

LAMA2-related muscular dystrophy Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.9
DANN	Benign	0.89

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: rs34997144; hg19: chr6-129813508;