rs1047981

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005562.3(LAMC2):c.2688G>A(p.Gln896Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,613,376 control chromosomes in the GnomAD database, including 46,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8133 hom., cov: 32)

Exomes 𝑓: 0.21 ( 37989 hom. )

Consequence

LAMC2
NM_005562.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.360

Variant links:

Genes affected

LAMC2 (HGNC:6493): (laminin subunit gamma 2) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), have a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 2. The gamma 2 chain, formerly thought to be a truncated version of beta chain (B2t), is highly homologous to the gamma 1 chain; however, it lacks domain VI, and domains V, IV and III are shorter. It is expressed in several fetal tissues but differently from gamma 1, and is specifically localized to epithelial cells in skin, lung and kidney. The gamma 2 chain together with alpha 3 and beta 3 chains constitute laminin 5 (earlier known as kalinin), which is an integral part of the anchoring filaments that connect epithelial cells to the underlying basement membrane. The epithelium-specific expression of the gamma 2 chain implied its role as an epithelium attachment molecule, and mutations in this gene have been associated with junctional epidermolysis bullosa, a skin disease characterized by blisters due to disruption of the epidermal-dermal junction. Two transcript variants resulting from alternative splicing of the 3' terminal exon, and encoding different isoforms of gamma 2 chain, have been described. The two variants are differentially expressed in embryonic tissues, however, the biological significance of the two forms is not known. Transcript variants utilizing alternative polyA_signal have also been noted in literature. [provided by RefSeq, Aug 2011]

LAMC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-183237438-G-A is Benign according to our data. Variant chr1-183237438-G-A is described in ClinVar as [Benign]. Clinvar id is 259786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-183237438-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.36 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMC2	NM_005562.3 link	c.2688G>A	p.Gln896Gln	synonymous_variant	Exon 18 of 23	ENST00000264144.5	NP_005553.2	Q13753-1
LAMC2	NM_018891.3 link	c.2688G>A	p.Gln896Gln	synonymous_variant	Exon 18 of 22		NP_061486.2	Q13753-2
LAMC2	XM_047420358.1 link	c.2688G>A	p.Gln896Gln	synonymous_variant	Exon 18 of 24		XP_047276314.1
LAMC2	XM_047420361.1 link	c.2688G>A	p.Gln896Gln	synonymous_variant	Exon 18 of 23		XP_047276317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMC2	ENST00000264144.5 link	c.2688G>A	p.Gln896Gln	synonymous_variant	Exon 18 of 23	1	NM_005562.3	ENSP00000264144.4		Q13753-1
LAMC2	ENST00000493293.5 link	c.2688G>A	p.Gln896Gln	synonymous_variant	Exon 18 of 22	1		ENSP00000432063.1		Q13753-2

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44418

AN:

152002

Hom.:

8099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.179

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.258

AC:

64719

AN:

251246

Hom.:

9965

AF XY:

0.248

AC XY:

33653

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.511

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.343

Gnomad SAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.213

AC:

311566

AN:

1461256

Hom.:

37989

Cov.:

AF XY:

0.214

AC XY:

155811

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.394

Gnomad4 SAS exome

AF:

0.312

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.293

AC:

44518

AN:

152120

Hom.:

8133

Cov.:

AF XY:

0.293

AC XY:

21783

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.312

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.179

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.235

Hom.:

3948

Bravo

AF:

0.311

Asia WGS

AF:

0.341

AC:

1184

AN:

3478

EpiCase

AF:

0.171

EpiControl

AF:

0.169

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 27, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15370542, 11279058) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Junctional epidermolysis bullosa

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

-0.92

CADD

Benign

0.20

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over