Variant 6-129464246-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000426.4(LAMA2):c.6993-44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,545,330 control chromosomes in the GnomAD database, including 279,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32749 hom., cov: 31)

Exomes 𝑓: 0.59 ( 246378 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.72

Variant links:

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 links:

ENSG00000226149 (HGNC:):

ENSG00000226149 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-129464246-T-C is Benign according to our data. Variant chr6-129464246-T-C is described in ClinVar as [Benign]. Clinvar id is 256084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129464246-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA2	NM_000426.4 linkuse as main transcript	c.6993-44T>C		intron_variant		ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 linkuse as main transcript	c.6993-44T>C		intron_variant			NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA2	ENST00000421865.3 linkuse as main transcript	c.6993-44T>C		intron_variant		5	NM_000426.4	ENSP00000400365.2		P24043

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98143

AN:

151622

Hom.:

32701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.703

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.621

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.610

AC:

152214

AN:

249648

Hom.:

47133

AF XY:

0.605

AC XY:

81609

AN XY:

134944

show subpopulations

Gnomad AFR exome

AF:

0.825

Gnomad AMR exome

AF:

0.648

Gnomad ASJ exome

AF:

0.624

Gnomad EAS exome

AF:

0.553

Gnomad SAS exome

AF:

0.634

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.594

GnomAD4 exome

AF:

0.592

AC:

825441

AN:

1393590

Hom.:

246378

Cov.:

AF XY:

0.592

AC XY:

412991

AN XY:

697274

show subpopulations

Gnomad4 AFR exome

AF:

0.831

Gnomad4 AMR exome

AF:

0.650

Gnomad4 ASJ exome

AF:

0.625

Gnomad4 EAS exome

AF:

0.537

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.568

Gnomad4 NFE exome

AF:

0.581

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.648

AC:

98257

AN:

151740

Hom.:

32749

Cov.:

AF XY:

0.645

AC XY:

47861

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.815

Gnomad4 AMR

AF:

0.624

Gnomad4 ASJ

AF:

0.615

Gnomad4 EAS

AF:

0.541

Gnomad4 SAS

AF:

0.623

Gnomad4 FIN

AF:

0.549

Gnomad4 NFE

AF:

0.577

Gnomad4 OTH

AF:

0.625

Alfa

AF:

0.590

Hom.:

40539

Bravo

AF:

0.661

Asia WGS

AF:

0.573

AC:

1992

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.36

DANN

Benign

0.44

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

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