dbSNP rs11967042: LAMA2:c.3037+49G>A (chr6-129297914-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000426.4(LAMA2):c.3037+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,504,734 control chromosomes in the GnomAD database, including 11,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1433 hom., cov: 33)

Exomes 𝑓: 0.10 ( 9632 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.36

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 6-129297914-G-A is Benign according to our data. Variant chr6-129297914-G-A is described in ClinVar as [Benign]. Clinvar id is 256063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129297914-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA2	NM_000426.4 link	c.3037+49G>A		intron_variant	Intron 21 of 64	ENST00000421865.3	NP_000417.3
LAMA2	NM_001079823.2 link	c.3037+49G>A		intron_variant	Intron 21 of 63		NP_001073291.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA2	ENST00000421865.3 link	c.3037+49G>A	intron_variant	Intron 21 of 64	5	NM_000426.4	ENSP00000400365.2	P24043
LAMA2	ENST00000618192.5 link	c.3301+49G>A	intron_variant	Intron 22 of 65	5		ENSP00000480802.2	A0A087WX80
LAMA2	ENST00000617695.5 link	c.3037+49G>A	intron_variant	Intron 21 of 63	5		ENSP00000481744.2	A0A087WYF1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17728

AN:

151976

Hom.:

1430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.201

Gnomad ASJ

AF:

0.0972

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0791

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.143

AC:

30729

AN:

214394

Hom.:

3194

AF XY:

0.135

AC XY:

15562

AN XY:

114978

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.277

Gnomad ASJ exome

AF:

0.0966

Gnomad EAS exome

AF:

0.390

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.0800

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.102

AC:

137753

AN:

1352640

Hom.:

9632

Cov.:

AF XY:

0.101

AC XY:

68130

AN XY:

676048

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.267

Gnomad4 ASJ exome

AF:

0.0990

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.0816

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.117

AC:

17749

AN:

152094

Hom.:

1433

Cov.:

AF XY:

0.123

AC XY:

9121

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.0972

Gnomad4 EAS

AF:

0.401

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0791

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.102

Hom.:

304

Bravo

AF:

0.126

Asia WGS

AF:

0.202

AC:

706

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 18, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.093

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