6-129454325-T-C

Variant summary

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

The NM_000426.4(LAMA2):​c.6707+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,558,298 control chromosomes in the GnomAD database, including 15,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1656 hom., cov: 32)
Exomes 𝑓: 0.14 ( 13707 hom. )

Consequence

LAMA2
NM_000426.4 intron

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -2.08
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]

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=-0.82).
BP6
Variant 6-129454325-T-C is Benign according to our data. Variant chr6-129454325-T-C is described in ClinVar as [Benign]. Clinvar id is 256083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-129454325-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LAMA2NM_000426.4 linkuse as main transcriptc.6707+37T>C intron_variant ENST00000421865.3
LAMA2NM_001079823.2 linkuse as main transcriptc.6707+37T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LAMA2ENST00000421865.3 linkuse as main transcriptc.6707+37T>C intron_variant 5 NM_000426.4
ENST00000665046.1 linkuse as main transcriptn.976-13073A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.143
AC:
21723
AN:
152014
Hom.:
1658
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.131
Gnomad AMI
AF:
0.247
Gnomad AMR
AF:
0.185
Gnomad ASJ
AF:
0.101
Gnomad EAS
AF:
0.211
Gnomad SAS
AF:
0.161
Gnomad FIN
AF:
0.149
Gnomad MID
AF:
0.117
Gnomad NFE
AF:
0.134
Gnomad OTH
AF:
0.150
GnomAD3 exomes
AF:
0.157
AC:
36107
AN:
229938
Hom.:
2935
AF XY:
0.153
AC XY:
19086
AN XY:
124380
show subpopulations
Gnomad AFR exome
AF:
0.136
Gnomad AMR exome
AF:
0.217
Gnomad ASJ exome
AF:
0.0989
Gnomad EAS exome
AF:
0.226
Gnomad SAS exome
AF:
0.157
Gnomad FIN exome
AF:
0.162
Gnomad NFE exome
AF:
0.134
Gnomad OTH exome
AF:
0.151
GnomAD4 exome
AF:
0.136
AC:
191826
AN:
1406166
Hom.:
13707
Cov.:
23
AF XY:
0.137
AC XY:
95924
AN XY:
701884
show subpopulations
Gnomad4 AFR exome
AF:
0.127
Gnomad4 AMR exome
AF:
0.212
Gnomad4 ASJ exome
AF:
0.0949
Gnomad4 EAS exome
AF:
0.203
Gnomad4 SAS exome
AF:
0.153
Gnomad4 FIN exome
AF:
0.159
Gnomad4 NFE exome
AF:
0.129
Gnomad4 OTH exome
AF:
0.144
GnomAD4 genome
AF:
0.143
AC:
21727
AN:
152132
Hom.:
1656
Cov.:
32
AF XY:
0.144
AC XY:
10729
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.131
Gnomad4 AMR
AF:
0.185
Gnomad4 ASJ
AF:
0.101
Gnomad4 EAS
AF:
0.211
Gnomad4 SAS
AF:
0.161
Gnomad4 FIN
AF:
0.149
Gnomad4 NFE
AF:
0.134
Gnomad4 OTH
AF:
0.147
Alfa
AF:
0.130
Hom.:
240
Bravo
AF:
0.145
Asia WGS
AF:
0.163
AC:
568
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
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
1.2
DANN
Benign
0.58

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.

Other links and lift over

dbSNP: rs2297742; hg19: chr6-129775470; COSMIC: COSV70351263; API