rs2297738

Variant names:

• chr6-129440967-G-A
• rs2297738
• NM_000426.4:c.6237G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-129440967-G-A
• chr6-129440967-G-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.6237G>A​(p.Thr2079Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,612,810 control chromosomes in the GnomAD database, including 21,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2159 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19787 hom.)
• Consequence: LAMA2 NM_000426.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.70

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=-0.56).
• BP6: Variant 6-129440967-G-A is Benign according to our data. Variant chr6-129440967-G-A is described in ClinVar as [Benign]. Clinvar id is 92975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129440967-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 65	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 64		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 65	5	NM_000426.4	ENSP00000400365.2
LAMA2	ENST00000618192.5	c.6501G>A	p.Thr2167Thr	synonymous_variant	Exon 44 of 66	5		ENSP00000480802.2
LAMA2	ENST00000617695.5	c.6237G>A	p.Thr2079Thr	synonymous_variant	Exon 43 of 64	5		ENSP00000481744.2
ENSG00000226149	ENST00000665046.1	n.1261C>T		non_coding_transcript_exon_variant	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24773 AN: 152000 Hom.: 2159 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.163

GnomAD3 exomes AF: 0.173 AC: 43412 AN: 250786 Hom.: 3973 AF XY: 0.171 AC XY: 23144 AN XY: 135544

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.220

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.217

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.214

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.163 AC: 237679 AN: 1460692 Hom.: 19787 Cov.: 33 AF XY: 0.163 AC XY: 118245 AN XY: 726738

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.163 AC: 24777 AN: 152118 Hom.: 2159 Cov.: 32 AF XY: 0.167 AC XY: 12387 AN XY: 74362

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.160

Alfa AF: 0.151 Hom.: 2370

Bravo AF: 0.161

Asia WGS AF: 0.175 AC: 609 AN: 3478

EpiCase AF: 0.155

EpiControl AF: 0.158

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Jan 20, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

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 05, 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

- -

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 12, 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	-0.56
CADD	Benign	8.4
DANN	Benign	0.62

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: rs2297738; hg19: chr6-129762112; COSMIC: COSV70344022; COSMIC: COSV70344022;